Author: "Pénicaud, A" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

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221 results on '"Pénicaud, A"'

1. Pain sensing neurons promote tissue regeneration in adult mice

Author: Lise Rabiller, Elodie Labit, Christophe Guissard, Silveric Gilardi, Bruno P. Guiard, Lionel Moulédous, Marine Silva, Gilles Mithieux, Luc Pénicaud, Anne Lorsignol, Louis Casteilla, and Cécile Dromard
Subjects: Medicine
Abstract: Abstract Tissue repair after injury in adult mammals, usually results in scarring and loss of function in contrast to lower vertebrates such as the newt and zebrafish that regenerate. Understanding the regulatory processes that guide the outcome of tissue repair is therefore a concerning challenge for regenerative medicine. In multiple regenerative animal species, the nerve dependence of regeneration is well established, but the nature of the innervation required for tissue regeneration remains largely undefined. Using our model of induced adipose tissue regeneration in adult mice, we demonstrate here that nociceptive nerves promote regeneration and their removal impairs tissue regeneration. We also show that blocking the receptor for the nociceptive neuropeptide calcitonin gene-related peptide (CGRP) inhibits regeneration, whereas CGRP administration induces regeneration. These findings reveal that peptidergic nociceptive neurons are required for adult mice tissue regeneration.
Published: 2021
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2. Driving regeneration, instead of healing, in adult mammals: the decisive role of resident macrophages through efferocytosis

Author: Lise Rabiller, Virginie Robert, Adèle Arlat, Elodie Labit, Marielle Ousset, Marie Salon, Agnès Coste, Léa Da Costa-Fernandes, Paul Monsarrat, Bruno Ségui, Mireille André, Christophe Guissard, Marie-Laure Renoud, Marine Silva, Gilles Mithieux, Isabelle Raymond-Letron, Luc Pénicaud, Anne Lorsignol, Louis Casteilla, Cécile Dromard Berthézène, and Béatrice Cousin
Subjects: Medicine
Abstract: Abstract Tissue repair after lesion usually leads to scar healing and thus loss of function in adult mammals. In contrast, other adult vertebrates such as amphibians have the ability to regenerate and restore tissue homeostasis after lesion. Understanding the control of the repair outcome is thus a concerning challenge for regenerative medicine. We recently developed a model of induced tissue regeneration in adult mice allowing the comparison of the early steps of regenerative and scar healing processes. By using studies of gain and loss of function, specific cell depletion approaches, and hematopoietic chimeras we demonstrate here that tissue regeneration in adult mammals depends on an early and transient peak of granulocyte producing reactive oxygen species and an efficient efferocytosis specifically by tissue-resident macrophages. These findings highlight key and early cellular pathways able to drive tissue repair towards regeneration in adult mammals.
Published: 2021
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3. Modulation of large dense core vesicle insulin content mediates rhythmic hormone release from pancreatic beta cells over the 24h cycle.

Author: Aurore Quinault, Corinne Leloup, Geoffrey Denwood, Coralie Spiegelhalter, Marianne Rodriguez, Philippe Lefebvre, Nadia Messaddeq, Quan Zhang, Catherine Dacquet, Luc Pénicaud, and Stephan C Collins
Subjects: Medicine, Science
Abstract: The rhythmic nature of insulin secretion over the 24h cycle in pancreatic islets has been mostly investigated using transcriptomics studies showing that modulation of insulin secretion over this cycle is achieved via distal stages of insulin secretion. We set out to measure β-cell exocytosis using in depth cell physiology techniques at several time points. In agreement with the activity and feeding pattern of nocturnal rodents, we find that C57/Bl6J islets in culture for 24h exhibit higher insulin secretion during the corresponding dark phase than in the light phase (Zeitgeber Time ZT20 and ZT8, respectively, in vivo). Glucose-induced insulin secretion is increased by 21% despite normal intracellular Ca2+ transients and depolarization-evoked exocytosis, as measured by whole-cell capacitance measurements. This paradox is explained by a 1.37-fold increase in beta cell insulin content. Ultramorphological analyses show that vesicle size and density are unaltered, demonstrating that intravesicular insulin content per granule is modulated over the 24h cycle. Proinsulin levels did not change between ZT8 and ZT20. Islet glucagon content was inversely proportional to insulin content indicating that this unique feature is likely to support a physiological role. Microarray data identified the differential expression of 301 transcripts, of which 26 are miRNAs and 54 are known genes (including C2cd4b, a gene previously involved in insulin processing, and clock genes such as Bmal1 and Rev-erbα). Mouse β-cell secretion over the full course of the 24h cycle may rely on several distinct cellular functions but late night increase in insulin secretion depends solely on granule insulin content.
Published: 2018
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4. Driving regeneration, instead of healing, in adult mammals: the decisive role of resident macrophages through efferocytosis

Author: Anne Lorsignol, Isabelle Raymond-Letron, Léa Da Costa-Fernandes, Lise Rabiller, Béatrice Cousin, Marine Silva, Adèle Arlat, Elodie Labit, Paul Monsarrat, Agnès Coste, Bruno Ségui, Gilles Mithieux, Marie-Laure Renoud, Mireille André, Cécile Dromard Berthézène, Marie Salon, Luc Pénicaud, Virginie Robert, Marielle Ousset, Christophe Guissard, Louis Casteilla, STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada], Geroscience and rejuvenation research center (RESTORE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Calgary, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition, diabète et cerveau, Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Cell biology, Physiology, [SDV]Life Sciences [q-bio], Immunology, Biomedical Engineering, Medicine (miscellaneous), Granulocyte, Biology, Regenerative medicine, Article, Lesion, 03 medical and health sciences, 0302 clinical medicine, medicine, Efferocytosis, Tissue homeostasis, Loss function, 030304 developmental biology, 0303 health sciences, Regeneration (biology), 3. Good health, Haematopoiesis, medicine.anatomical_structure, Medicine, medicine.symptom, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Tissue repair after lesion usually leads to scar healing and thus loss of function in adult mammals. In contrast, other adult vertebrates such as amphibians have the ability to regenerate and restore tissue homeostasis after lesion. Understanding the control of the repair outcome is thus a concerning challenge for regenerative medicine. We recently developed a model of induced tissue regeneration in adult mice allowing the comparison of the early steps of regenerative and scar healing processes. By using studies of gain and loss of function, specific cell depletion approaches, and hematopoietic chimeras we demonstrate here that tissue regeneration in adult mammals depends on an early and transient peak of granulocyte producing reactive oxygen species and an efficient efferocytosis specifically by tissue-resident macrophages. These findings highlight key and early cellular pathways able to drive tissue repair towards regeneration in adult mammals.
Published: 2021

5. The INSPIRE research initiative: a program for GeroScience and healthy aging research going from animal models to humans and the healthcare system

Author: Louis Casteilla, Sandrine Andrieu, Pierre Payoux, Isabelle Ader, Cédric Dray, Bruno Vellas, Luc Pénicaud, Roland S. Liblau, Nathalie Vergnolle, P. de Souto Barreto, Yves Rolland, Sophie Guyonnet, Nicolas Fazilleau, Pierre Gourdy, Noélie Davezac, Angelo Parini, Philippe Valet, Claire Rampon, Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Region Auvergne-Rhone-Alpes, Region Bourgogne-Franche-Comte, Region Hauts-de-France, Region Nouvelle-Aquitaine (Reference number: 1901175), European Regional Development Fund (ERDF) (Project number: MP0022856), Inspire Chairs of Excellence - Alzheimer Prevention in Occitania and Catalonia (APOC), EDENIS, KORIAN, Pfizer, Pierre-Fabre, SEGUIN, Nathalie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI)
Subjects: 0301 basic medicine, Gerontology, Gerosciences, medicine.medical_specialty, Research program, Biomedical Research, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Delivery of Health Care, MESH: Geriatrics, Healthy Aging, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Medicine, MESH: Animals, intrinsic capacity, 030212 general & internal medicine, Healthy aging, Aged, MESH: Aged, Geriatrics, MESH: Humans, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Geroscience, business.industry, MESH: Biomedical Research, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Public health, MESH: Healthy Aging, General Medicine, Risk factor (computing), 3. Good health, Integrated care, 030104 developmental biology, MESH: Models, Animal, biological aging, Models, Animal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Translational science, business, Delivery of Health Care
Abstract: International audience; Aging is the most important risk factor for the onset of several chronic diseases and functional decline. Understanding the interplays between biological aging and the biology of diseases and functional loss as well as integrating a function-centered approach to the care pathway of older adults are crucial steps towards the elaboration of preventive strategies (both pharmacological and non-pharmacological) against the onset and severity of burdensome chronic conditions during aging. In order to tackle these two crucial challenges, ie, how both the manipulation of biological aging and the implementation of a function-centered care pathway (the Integrated Care for Older People (ICOPE) model of the World Health Organization) may contribute to the trajectories of healthy aging, a new initiative on Gerosciences was built: the INSPIRE research program. The present article describes the scientific background on which the foundations of the INSPIRE program have been constructed and provides the general lines of this initiative that involves researchers from basic and translational science, clinical gerontology, geriatrics and primary care, and public health.
Published: 2020

6. Physiological and biochemical responses of Yarrowia lipolytica to dehydration induced by air-drying and freezing.

Author: Caroline Pénicaud, Sophie Landaud, Frédéric Jamme, Pauline Talbot, Marielle Bouix, Sarrah Ghorbal, and Fernanda Fonseca
Subjects: Medicine, Science
Abstract: Organisms that can withstand anhydrobiosis possess the unique ability to temporarily and reversibly suspend their metabolism for the periods when they live in a dehydrated state. However, the mechanisms underlying the cell's ability to tolerate dehydration are far from being fully understood. The objective of this study was to highlight, for the first time, the cellular damage to Yarrowia lipolytica as a result of dehydration induced by drying/rehydration and freezing/thawing. Cellular response was evaluated through cell cultivability determined by plate counts, esterase activity and membrane integrity assessed by flow cytometry, and the biochemical composition of cells as determined by FT-IR spectroscopy. The effects of the harvesting time (in the log or stationary phase) and of the addition of a protective molecule, trehalose, were investigated. All freshly harvested cells exhibited esterase activity and no alteration of membrane integrity. Cells freshly harvested in the stationary phase presented spectral contributions suggesting lower nucleic acid content and thicker cell walls, as well as longer lipid chains than cells harvested in the log phase. Moreover, it was found that drying/rehydration induced cell plasma membrane permeabilization, loss of esterase activity with concomitant protein denaturation, wall damage and oxidation of nucleic acids. Plasma membrane permeabilization and loss of esterase activity could be reduced by harvesting in the stationary phase and/or with trehalose addition. Protein denaturation and wall damage could be reduced by harvesting in the stationary phase. In addition, it was shown that measurements of loss of membrane integrity and preservation of esterase activity were suitable indicators of loss and preservation of cultivability, respectively. Conversely, no clear effect of freezing/thawing could be observed, probably because of the favorable operating conditions applied. These results give insights into Y. lipolytica mechanisms of cellular response to dehydration and provide a basis to better understand its ability to tolerate anhydrobiosis.
Published: 2014
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7. Pain sensing neurons promote tissue regeneration in adult mice

Author: Anne Lorsignol, Gilles Mithieux, Christophe Guissard, Silveric Gilardi, Marine Silva, Lionel Moulédous, Elodie Labit, Louis Casteilla, Lise Rabiller, Luc Pénicaud, Cécile Dromard, Bruno P. Guiard, Geroscience and rejuvenation research center (RESTORE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, EFS, McGill University = Université McGill [Montréal, Canada], University of Calgary, Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Nutrition, diabète et cerveau (NUDICE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), and Di Carlo, Marie-Ange
Subjects: Regeneration (biology), Biomedical Engineering, Medicine (miscellaneous), Neuropeptide, Adipose tissue, Cell Biology, Calcitonin gene-related peptide, Biology, biology.organism_classification, Regenerative medicine, Article, Cell biology, Calcitonin, Medicine, Homeostasis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Peripheral nervous system, Receptor, Zebrafish, Developmental Biology
Abstract: Tissue repair after injury in adult mammals, usually results in scarring and loss of function in contrast to lower vertebrates such as the newt and zebrafish that regenerate. Understanding the regulatory processes that guide the outcome of tissue repair is therefore a concerning challenge for regenerative medicine. In multiple regenerative animal species, the nerve dependence of regeneration is well established, but the nature of the innervation required for tissue regeneration remains largely undefined. Using our model of induced adipose tissue regeneration in adult mice, we demonstrate here that nociceptive nerves promote regeneration and their removal impairs tissue regeneration. We also show that blocking the receptor for the nociceptive neuropeptide calcitonin gene-related peptide (CGRP) inhibits regeneration, whereas CGRP administration induces regeneration. These findings reveal that peptidergic nociceptive neurons are required for adult mice tissue regeneration.
Published: 2021

8. The INSPIRE bio-resource research platform for healthy aging and geroscience: focus on the human translational research cohort (the INSPIRE-t cohort)

Author: Yves Rolland, Sandrine Andrieu, Philippe Valet, P. de Souto Barreto, Pierre Gourdy, Sophie Guyonnet, Nicolas Fazilleau, Isabelle Ader, Claire Rampon, Louis Casteilla, Luc Pénicaud, Noélie Davezac, Angelo Parini, C. Takeda, Roland S. Liblau, Pierre-Jean Ousset, Pierre Payoux, Cédric Dray, Nathalie Vergnolle, Bruno Vellas, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Gérontopôle, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), STROMALab, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches sur la Cognition Animale - UMR5169 (CRCA), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toulouse Neuro Imaging Center (ToNIC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Institut de Recherche en Santé Digestive (IRSD ), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), The Region Auvergne-Rhone-Alpes, Region Bourgogne-Franche-Comte,Region Hauts-de-France,Region Nouvelle-Aquitaine (1901175), the European Regional Development Fund (ERDF) (Project number: MP0022856), MSD Avenir, Inspire Chairs of Excellence - Alzheimer Prevention in Occitania and Catalonia (APOC), EDENIS, KORIAN, Pfizer, Pierre-Fabre, European Project: ERDF, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), SEGUIN, Nathalie, and European Regional Development Fund - ERDF - INCOMING
Subjects: 0301 basic medicine, Gerontology, [SDV]Life Sciences [q-bio], MESH: Geriatrics, Cohort Studies, Healthy Aging, Translational Research, Biomedical, 0302 clinical medicine, MESH: Aged, 80 and over, biology of aging, Health care, Medicine, MESH: Cohort Studies, Biological Specimen Banks, Original Research, integrated care, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Geroscience, MESH: Biological Specimen Banks, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, MESH: Healthy Aging, General Medicine, Middle Aged, Biobank, 3. Good health, [SDV] Life Sciences [q-bio], biological aging, Cohort, Population study, France, MESH: Translational Research, Biomedical, Adult, Gerosciences, Translational research, 03 medical and health sciences, Humans, intrinsic capacity, Aged, MESH: Humans, business.industry, MESH: Adult, Integrated care, MESH: France, 030104 developmental biology, Geriatrics, translational research on aging, business, 030217 neurology & neurosurgery, Blood sampling
Abstract: International audience; Background : The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. Objectives : The main objective of the INStitute for Prevention healthy aging and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans.Methods : The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up.Expected Results : Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.Electronic Supplementary Material.Supplementary material : is available for this article at 10.14283/jfa.2020.38 and is accessible for authorized users.
Published: 2021

9. COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology

Author: Nicolas Meunier, Loïc Briand, Agnès Jacquin-Piques, Laurent Brondel, Luc Pénicaud, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), The Conseil Régional Bourgogne, Franche-Comté (PARI grant) and the FEDER (European Funding for Regional Economical Development)., Julien, Sabine, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Taste, 2019-20 coronavirus outbreak, Food intake, Coronavirus disease 2019 (COVID-19), [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Physiology, Anosmia, feeding behavior, Olfaction, Review, lcsh:Physiology, taste, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, smell, lcsh:QP1-981, business.industry, COVID-19, 3. Good health, Dysgeusia, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, medicine.symptom, physiopathology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Transduction (physiology), COVID 19, 030217 neurology & neurosurgery
Abstract: This article is part of the Research Topic "The Tribute of Physiology for the Understanding of COVID-19 Disease".; International audience; Smell and taste impairments are recognized as common symptoms in COVID 19 patients even in an asymptomatic phase. Indeed, depending on the country, in up to 85-90% of cases anosmia and dysgeusia are reported. We will review briefly the main mechanisms involved in the physiology of olfaction and taste focusing on receptors and transduction as well as the main neuroanatomical pathways. Then we will examine the current evidences, even if still fragmented and unsystematic, explaining the disturbances and mode of action of the virus at the level of the nasal and oral cavities. We will focus on its impact on the peripheral and central nervous system. Finally, considering the role of smell and taste in numerous physiological functions, especially in ingestive behavior, we will discuss the consequences on the physiology of the patients as well as management regarding food intake.
Published: 2021

10. Hemodialysis affects wanting and spontaneous intake of protein-rich foods in chronic kidney disease patients

Author: Yves Boirie, Anna Filancia, Luc Pénicaud, Eric Teillet, Agnès Jacquin-Piques, Marie-Claude Brindisi, Noureddine Hafnaoui, Christiane Mousson, Corinne Leloup, Laurent Brondel, Thomas Mouillot, Virginie Van Wymelbeke, Ioanna Meintani, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Grants from the Fondation Transplantation, Saint Apollinaire, France, from the Centre National de la Recherche Scientifique (CNRS), France, from the Association Bourguignonne pour le Développement de la Recherche et de la Formation en Néphrologie, Dialyse et Transplantation (NDT), Dijon, France, and from the Regional Council of Burgundy (PARI 2 Sensorialité)., Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, medicine.medical_treatment, 030232 urology & nephrology, Medicine (miscellaneous), Physiology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Reward, Renal Dialysis, medicine, Humans, In patient, Risk factor, Renal Insufficiency, Chronic, Wasting, Dialysis, 2. Zero hunger, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, digestive, oral, and skin physiology, Healthy subjects, medicine.disease, 3. Good health, Nephrology, Hemodialysis, medicine.symptom, business, Energy Intake, Kidney disease, Hormone
Abstract: Protein-energy wasting is a risk factor for mortality and morbidity in hemodialysis patients (HD patients). Food intake could be modified by HD-related changes in the food reward system (i.e., liking and wanting of specific macronutrients). In HD patients on days with and without dialysis, we evaluated (1) the reward system for protein-, fat-, and carbohydrate-rich foods, plasma hormones, and metabolite changes; and (2) the spontaneous ad libitum intake of macronutrients.Twenty-four HD patients evaluated their liking and wanting of macronutrients at 7:30 AM and 11:30 AM on a day with and a day without dialysis. Concentrations of hormones and plasma amino acids were determined. An additional 18 HD patients ate what they wanted from a buffet lunch comprising 8 dishes on a day with and a day without dialysis. Healthy subjects, age-, sex-, and body mass index-matched, served as controls.At 11:30 AM, wanting for protein-rich foods was higher on the day with than on the day without dialysis (P .01), bringing wanting levels close to those of healthy subjects. This increase correlated with changes in the concentrations of plasma amino acids (P .01). HD patients ate more protein from the buffet on the day with than on the day without dialysis (P .01) and more than healthy subjects (P .01).In HD patients, wanting and spontaneous intake of protein-rich foods increase immediately after dialysis. This increase correlated with decreased concentrations of plasma amino acids. Thus, in clinical practice, protein-rich foods should be recommended during and after dialysis in patients with protein-energy wasting.
Published: 2021

11. Tissue Regeneration: The Dark Side of Opioids

Author: Anne Lorsignol, Cécile Dromard Berthézène, Béatrice Cousin, Louis Casteilla, Géraldine Jourdan, Luc Pénicaud, Lise Rabiller, Geroscience and rejuvenation research center (RESTORE), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), McGill University = Université McGill [Montréal, Canada], and Cousin, Béatrice
Subjects: 0301 basic medicine, Standard of care, QH301-705.5, Analgesic, Pain, Context (language use), Review, Bioinformatics, opioid receptors, Catalysis, Inorganic Chemistry, 03 medical and health sciences, 0302 clinical medicine, Managing pain, Medicine, Animals, Humans, Pain Management, tissue repair, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, Spectroscopy, Wound Healing, Nerve activity, business.industry, Regeneration (biology), Organic Chemistry, opioids, General Medicine, Tissue repair, Regenerative process, 3. Good health, Computer Science Applications, Analgesics, Opioid, Chemistry, 030104 developmental biology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, regeneration, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, 030217 neurology & neurosurgery
Abstract: International audience; Opioids are regarded as among the most effective analgesic drugs and their use for the management of pain is considered standard of care. Despite their systematic administration in the peri-operative period, their impact on tissue repair has been studied mainly in the context of scar healing and is only beginning to be documented in the context of true tissue regeneration. Indeed, in mammals, growing evidence shows that opioids direct tissue repair towards scar healing, with a loss of tissue function, instead of the regenerative process that allows for recovery of both the morphology and function of tissue. Here, we review recent studies that highlight how opioids may prevent a regenerative process by silencing nociceptive nerve activity and a powerful anti-inflammatory effect. These data open up new perspectives for inducing tissue regeneration and argue for opioid-restricted strategies for managing pain associated with tissue injury.
Published: 2021

12. Fatty acid transporter CD36 mediates hypothalamic effect of fatty acids on food intake in rats.

Author: Valentine S Moullé, Christelle Le Foll, Erwann Philippe, Nadim Kassis, Claude Rouch, Nicolas Marsollier, Linh-Chi Bui, Christophe Guissard, Julien Dairou, Anne Lorsignol, Luc Pénicaud, Barry E Levin, Céline Cruciani-Guglielmacci, and Christophe Magnan
Subjects: Medicine, Science
Abstract: Variations in plasma fatty acid (FA) concentrations are detected by FA sensing neurons in specific brain areas such as the hypothalamus. These neurons play a physiological role in the control of food intake and the regulation of hepatic glucose production. Le Foll et al. previously showed in vitro that at least 50% of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to the interaction of long chain FA with FA translocase/CD36 (CD36). The present work assessed whether in vivo effects of hypothalamic FA sensing might be partly mediated by CD36 or intracellular events such as acylCoA synthesis or β-oxidation. To that end, a catheter was implanted in the carotid artery toward the brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5 h, then 10 min infusions of triglyceride emulsion, Intralipid +/- heparin (IL, IL(H), respectively) or saline/heparin (SH) were carried out and food intake was assessed over the next 5 h. Experimental groups included: 1) Rats previously injected in ventromedian nucleus (VMN) with shRNA against CD36 or scrambled RNA; 2) Etomoxir (CPT1 inhibitor) or saline co-infused with IL(H)/S(H); and 3) Triacsin C (acylCoA synthase inhibitor) or saline co-infused with IL(H)/S(H). IL(H) significantly lowered food intake during refeeding compared to S(H) (p
Published: 2013
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13. Cerebral cell renewal in adult mice controls the onset of obesity.

Author: Alexandra Gouazé, Xavier Brenachot, Caroline Rigault, Alice Krezymon, Camille Rauch, Emmanuelle Nédélec, Aleth Lemoine, Jean Gascuel, Sylvian Bauer, Luc Pénicaud, and Alexandre Benani
Subjects: Medicine, Science
Abstract: The hypothalamus plays a crucial role in the control of the energy balance and also retains neurogenic potential into adulthood. Recent studies have reported the severe alteration of the cell turn-over in the hypothalamus of obese animals and it has been proposed that a neurogenic deficiency in the hypothalamus could be involved in the development of obesity. To explore this possibility, we examined hypothalamic cell renewal during the homeostatic response to dietary fat in mice, i.e., at the onset of diet-induced obesity. We found that switching to high-fat diet (HFD) accelerated cell renewal in the hypothalamus through a local, rapid and transient increase in cell proliferation, peaking three days after introducing the HFD. Blocking HFD-induced cell proliferation by central delivery of an antimitotic drug prevented the food intake normalization observed after HFD introduction and accelerated the onset of obesity. This result showed that HFD-induced dividing brain cells supported an adaptive anorectic function. In addition, we found that the percentage of newly generated neurons adopting a POMC-phenotype in the arcuate nucleus was increased by HFD. This observation suggested that the maturation of neurons in feeding circuits was nutritionally regulated to adjust future energy intake. Taken together, these results showed that adult cerebral cell renewal was remarkably responsive to nutritional conditions. This constituted a physiological trait required to prevent severe weight gain under HFD. Hence this report highlighted the amazing plasticity of feeding circuits and brought new insights into our understanding of the nutritional regulation of the energy balance.
Published: 2013
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14. Hypothalamic S-nitrosylation contributes to the counter-regulatory response impairment following recurrent hypoglycemia.

Author: Xavier Fioramonti, Adam Deak, Srinidhi Deshpande, Lionel Carneiro, Chunxue Zhou, Nazish Sayed, Branly Orban, Joshua R Berlin, Luc Pénicaud, Corinne Leloup, Annie Beuve, and Vanessa H Routh
Subjects: Medicine, Science
Abstract: Hypoglycemia is a severe side effect of intensive insulin therapy. Recurrent hypoglycemia (RH) impairs the counter-regulatory response (CRR) which restores euglycemia. During hypoglycemia, ventromedial hypothalamus (VMH) production of nitric oxide (NO) and activation of its receptor soluble guanylyl cyclase (sGC) are critical for the CRR. Hypoglycemia also increases brain reactive oxygen species (ROS) production. NO production in the presence of ROS causes protein S-nitrosylation. S-nitrosylation of sGC impairs its function and induces desensitization to NO. We hypothesized that during hypoglycemia, the interaction between NO and ROS increases VMH sGC S-nitrosylation levels and impairs the CRR to subsequent episodes of hypoglycemia. VMH ROS production and S-nitrosylation were quantified following three consecutive daily episodes of insulin-hypoglycemia (RH model). The CRR was evaluated in rats in response to acute insulin-induced hypoglycemia or via hypoglycemic-hyperinsulinemic clamps. Pretreatment with the anti-oxidant N-acetyl-cysteine (NAC) was used to prevent increased VMH S-nitrosylation.Acute insulin-hypoglycemia increased VMH ROS levels by 49±6.3%. RH increased VMH sGC S-nitrosylation. Increasing VMH S-nitrosylation with intracerebroventricular injection of the nitrosylating agent S-nitroso-L-cysteine (CSNO) was associated with decreased glucagon secretion during hypoglycemic clamp. Finally, in RH rats pre-treated with NAC (0.5% in drinking water for 9 days) hypoglycemia-induced VMH ROS production was prevented and glucagon and epinephrine production was not blunted in response to subsequent insulin-hypoglycemia.These data suggest that NAC may be clinically useful in preventing impaired CRR in patients undergoing intensive-insulin therapy.
Published: 2013
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15. Mitochondrial Dynamin-Related Protein 1 (DRP1) translocation in response to cerebral glucose is impaired in a rat model of early alteration in hypothalamic glucose sensing

Author: Sylvie Grall, Claire Fenech, Chloé Chrétien, Lucie Desmoulins, Claude Knauf, Xavier Fioramonti, Anne Galinier, Christophe Magnan, Lionel Carneiro, Luc Pénicaud, Camille Allard, Audren Fournel, Stephan Collins, Corinne Leloup, Thomas Mouillot, Romain Paccoud, Fabienne Liénard, Céline Cruciani-Guglielmacci, Aurore Quinault, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine [Rangueil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Laboratoire de physiopathologie de la nutrition (LPN), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Développement et Communication Chimique chez les Insectes (DCCI), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Unité de Biologie Fonctionnelle et Adaptative [Avant 2020] (BFA (UMR_8251 / U1133)), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by a PhD fellowship from the Ministere de l'Enseignement Superieur et de la Recherche to LD and grants to CL: Institut de France (NRJ award), Agence National de la Recherche No ANR-11-BSV1-0007, recurrent financial supports from the Burgundy's Regional Council, the University of Burgundy and the CNRS. CCG and CM received grant from the Agence Nationale de la Recherche No ANR-16-CE14-0026., Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Pénicaud, Luc
Subjects: 0301 basic medicine, Blood Glucose, Male, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Mitochondrion, Energy homeostasis, DNM1L, 0302 clinical medicine, AMP-Activated Protein Kinase Kinases, Insulin-Secreting Cells, Insulin Secretion, Premovement neuronal activity, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, chemistry.chemical_classification, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Chemistry, Mitochondrial fission, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Mitochondria, [SDV] Life Sciences [q-bio], Protein Transport, Carotid Arteries, Hypothalamus, Glucose sensing, Original Article, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Signal Transduction, Dynamins, medicine.medical_specialty, endocrine system, lcsh:Internal medicine, Sensory Receptor Cells, 030209 endocrinology & metabolism, DRP1, 03 medical and health sciences, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rats, Wistar, lcsh:RC31-1245, Molecular Biology, Reactive oxygen species, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, AMPK, Cell Biology, Rats, ROS signaling, 030104 developmental biology, Endocrinology, Reactive Oxygen Species, Protein Kinases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective Hypothalamic glucose sensing (HGS) initiates insulin secretion (IS) via a vagal control, participating in energy homeostasis. This requires mitochondrial reactive oxygen species (mROS) signaling, dependent on mitochondrial fission, as shown by invalidation of the hypothalamic DRP1 protein. Here, our objectives were to determine whether a model with a HGS defect induced by a short, high fat-high sucrose (HFHS) diet in rats affected the fission machinery and mROS signaling within the mediobasal hypothalamus (MBH). Methods Rats fed a HFHS diet for 3 weeks were compared with animals fed a normal chow. Both in vitro (calcium imaging) and in vivo (vagal nerve activity recordings) experiments to measure the electrical activity of isolated MBH gluco-sensitive neurons in response to increased glucose level were performed. In parallel, insulin secretion to a direct glucose stimulus in isolated islets vs. insulin secretion resulting from brain glucose stimulation was evaluated. Intra-carotid glucose load-induced hypothalamic DRP1 translocation to mitochondria and mROS (H2O2) production were assessed in both groups. Finally, compound C was intracerebroventricularly injected to block the proposed AMPK-inhibited DRP1 translocation in the MBH to reverse the phenotype of HFHS fed animals. Results Rats fed a HFHS diet displayed a decreased HGS-induced IS. Responses of MBH neurons to glucose exhibited an alteration of their electrical activity, whereas glucose-induced insulin secretion in isolated islets was not affected. These MBH defects correlated with a decreased ROS signaling and glucose-induced translocation of the fission protein DRP1, as the vagal activity was altered. AMPK-induced inhibition of DRP1 translocation increased in this model, but its reversal through the injection of the compound C, an AMPK inhibitor, failed to restore HGS-induced IS. Conclusions A hypothalamic alteration of DRP1-induced fission and mROS signaling in response to glucose was observed in HGS-induced IS of rats exposed to a 3 week HFHS diet. Early hypothalamic modifications of the neuronal activity could participate in a primary defect of the control of IS and ultimately, the development of diabetes., Graphical abstract Image 1, Highlights • Only three weeks of HFHS diet consumption impairs hypothalamic glucose sensing. • HFHS consumption alters central glucose-induced vagal control of insulin secretion. • Glucose-induced ROS production and mitochondrial fission are decreased in HFHS rats. • Impaired translocation of DRP1in HFHS rats does not involve its phosphorylation.
Published: 2019

16. Role of Mitochondria in Brain Nutrient Sensing: Control of Energy Balance and Dysregulation in Obesity and Type 2 Diabetes

Author: Corinne Leloup, Luc Pénicaud, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Fédérale Toulouse Midi-Pyrénées, B. Morio, Luc Pénicaud, and M. Rigoulet
Subjects: nutrient sensing, medicine.medical_specialty, Central nervous system, Hindbrain, Type 2 diabetes, Nutrient sensing, Mitochondrion, Biology, mitochondrial reactive oxygen species, 03 medical and health sciences, 0302 clinical medicine, synaptic vesicles, Internal medicine, medicine, hypothalamus, 030304 developmental biology, 0303 health sciences, Arc (protein), medicine.disease, mitochondria, Endocrinology, medicine.anatomical_structure, Hypothalamus, astroglial mitochondria, metabolic regulation, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Homeostasis
Abstract: International audience; During the last 20 years, studies have revealed the important role of the central nervous system (CNS) in the regulation of homeostatic mechanisms, including food intake, energy expenditure, and glucose, lipid and protein homeostasis. Brain regions involved in the regulation of energy balance, such as the arcuate (ARC), the ventromedial nuclei of the hypothalamus (VMN), and the hindbrain, have the ability to monitor the amount of available fuel in the body, to modulate energy intake and expenditure, and to modify peripheral tissue/organ function via alteration of neuronal firing. For that, they must be informed about the level of nutrients. Within specific brain sites, neuronal populations have been described as able to sense all types of nutrients, enabling proper peripheral tissue adaptations to the fluctuating nutrient environment. Therefore, when glucose or fatty acids rise in the blood because of food consumption, specific brain circuits promote cessation of feeding (satiety), insulin secretion, and glucose use by peripheral tissues while inhibiting hepatic glucose production. When the level of glucose decreases between meals, however, another set of neurons is activated to promote hunger and appropriate changes in peripheral glucose and lipid metabolisms.
Published: 2019

17. Lactate fluxes mediated by the monocarboxylate transporter-1 are key determinants of the metabolic activity of beige adipocytes

Author: Jean-Charles Portais, Cedric Moro, Anne Galinier, Corinne Barreau, Edward T. Chouchani, Christophe Guissard, Isabelle Ader, Luc Pénicaud, Yannick Jeanson, Edern Cahoreau, Damien Lagarde, Anne-Karine Bouzier-Sore, Lindsay Peyriga, Luc Pellerin, Audrey Carrière, Louis Casteilla, Emmanuelle Arnaud, STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Biotiques et Santé Végétale, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Purpan (CHU Purpan), Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), European Commission MP0022856, ANR-18-CE18-0006,hiPSC-Adipospheres,Un modèle 3D d'adipocytes beiges dérivés de cellules iPS humaines pour le criblage de molécules et pour la thérapie cellulaire de l'obésité(2018), ANR-10-LABX-0057,TRAIL,Translational Research and Advanced Imaging Laboratory(2010), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul FluxoMet (TBI-MetaToul), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and Résonance Magnétique des Systèmes Biologiques (CRMSB)
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Adipose tissue, White adipose tissue, Biochemistry, chemistry.chemical_compound, Mice, glycolysis as Manuscript RA120.016303, Adipocyte, Brown adipose tissue, Uncoupling protein, Glycolysis, Adipocytes, Beige, monocarboxylate transporters, ComputingMilieux_MISCELLANEOUS, biology, Symporters, CL, CL316.243, Chemistry, Thermogenesis, glycolysis, Thermogenin, Cell biology, uncoupling protein-1, medicine.anatomical_structure, Monocarboxylate transporter 1, beige adipocytes, ANR, Agence Nationale pour la Recherche, LCM, laser capture microdissection, Signal Transduction, Research Article, Monocarboxylic Acid Transporters, AZD, AZD3965, uncoupling protein 1, 03 medical and health sciences, UCP1, uncoupling protein 1, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Lactic Acid, lactate fluxes, Molecular Biology, 030102 biochemistry & molecular biology, Mesenchymal Stem Cells, Cell Biology, Mice, Inbred C57BL, BAT, brown adipose tissue, 030104 developmental biology, Gene Expression Regulation, biology.protein, MCTs, monocarboxylate transporters
Abstract: International audience; Activation of energy-dissipating brown/beige adipocytes represents an attractive therapeutic strategy against metabolic disorders. While lactate is known to induce beiging through the regulation of Ucp1 gene expression, the role of lactate transporters on beige adipocytes' ongoing metabolic activity remains poorly understood. To explore the function of the lactate-transporting monocarboxylate transporters (MCTs), we used a combination of primary cell culture studies, C-13 isotopic tracing, laser microdissection experiments, and in situ immunofluorescence of murine adipose fat pads. Dissecting white adipose tissue heterogeneity revealed that the MCT1 is expressed in inducible beige adipocytes as the emergence of uncoupling protein 1 after cold exposure was restricted to a subpopulation of MCT1-expressing adipocytes suggesting MCT1 as a marker of inducible beige adipocytes. We also observed that MCT1 mediates bidirectional and simultaneous inward and outward lactate fluxes, which were required for efficient utilization of glucose by beige adipocytes activated by the canonical beta 3-adrenergic signaling pathway. Finally, we demonstrated that significant lactate import through MCT1 occurs even when glucose is not limiting, which feeds the oxidative metabolism of beige adipocytes. These data highlight the key role of lactate fluxes in finely tuning the metabolic activity of beige adipocytes according to extracellular metabolic conditions and reinforce the emerging role of lactate metabolism in the control of energy homeostasis.
Published: 2020

18. Highlighting Protective Effect of Encapsulation on Yeast Cell Response to Dehydration Using Synchrotron Infrared Microspectroscopy at the Single-Cell Level

Author: Fernanda Fonseca, Stéphane Guyot, Rémi Saurel, Florence Husson, Caroline Pénicaud, Christophe Sandt, Stéphanie Passot, Thanh Dat Nguyen, Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Procédés Microbiologiques et Biotechnologiques (PMB), Procédés Alimentaires et Microbiologiques (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Paris-Saclay Food and Bioproduct Engineering (SayFood), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SMIS Beamline, Synchrotron SOLEIL, Physico-Chimie de l'Aliment et du Vin (PCAV), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Conseil Regional de Bourgogne through the 'plan d'actions regional pour l'innovation' (PARI), European Project: PO FEDER-FSE Bourgogne 2014/2020, Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Microbiology (medical), Infrared, Kinetics, lcsh:QR1-502, yeast, Microbiology, lcsh:Microbiology, law.invention, 03 medical and health sciences, law, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Membrane fluidity, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Dehydration, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Original Research, 030304 developmental biology, 0303 health sciences, response, synchrotron FTIR, 030306 microbiology, Chemistry, Layer by layer, dehydration, medicine.disease, Yeast, Synchrotron, [CHIM.POLY]Chemical Sciences/Polymers, Biophysics, encapsulation, Cell response, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; In the present paper, the Layer by Layer (LbL) method using beta-lactoglobulin and sodium alginate was performed to individually encapsulateSaccharomyces cerevisiaecells in microorganized shells in order to protect them against stresses during dehydration. Higher survival (similar to 1 log) for encapsulated yeast cells was effectively observed after air dehydration at 45 degrees C. For the first time, the potentiality of Synchrotron-Fourier Transform InfraRed microspectroscopy (S-FTIR) was used at the single-cell level in order to analyze the contribution of the biochemical composition of non-encapsulated vs. encapsulated cells in response to dehydration. The microspectroscopy measurements clearly differentiated between non-encapsulated and encapsulated yeast cells in the amide band region. In the spectral region specific to lipids, the S-FTIR results indicated probably the decrease in membrane fluidity of yeast after dehydration without significant distinction between the two samples. These data suggested minor apparent chemical changes in cell attributable to the LbL system upon dehydration. More insights are expected regarding the lower mortality among encapsulated cells. Indeed the hypothesis that the biopolymeric layers could induce less damage in cell by affecting the transfer kinetics during dehydration-rehydration cycle, should be verified in further work.
Published: 2020

19. Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers.

Author: Marta Amigó-Correig, Sílvia Barceló-Batllori, Guadalupe Soria, Alice Krezymon, Alexandre Benani, Luc Pénicaud, Raúl Tudela, Anna Maria Planas, Eduardo Fernández, Maria del Carmen Carmona, and Ramon Gomis
Subjects: Medicine, Science
Abstract: ObjectiveThis study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism.MethodsAdult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed.ResultsSodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus.ConclusionsAltogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease.
Published: 2012
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20. Autonomic nervous system and pancreatic islet blood flow

Author: Luc Pénicaud
Subjects: 0301 basic medicine, endocrine system, 030209 endocrinology & metabolism, Biology, Autonomic Nervous System, Biochemistry, Islets of Langerhans, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, medicine, Animals, Humans, Secretion, Obesity, Insulin secretion, geography, geography.geographical_feature_category, General Medicine, Blood flow, Islet, medicine.disease, Autonomic nervous system, Diabetes Mellitus, Type 1, 030104 developmental biology, Diabetes Mellitus, Type 2, Regional Blood Flow, Immunology, Neuroscience
Abstract: Vascularization and innervation of the islet of Langerhans are highly interconnected and are critical for intercellular and intertissular communication. They are both involved in the control of islet blood flow which has been shown to have an important role in the control of endocine secretion. Both parameters are disturbed during the course of metabolic pathologies and particularly diabetes. A better understanding of these mechanisms has and will greatly benefit from the rapidly-emerging technologies particularly in vivo imaging enabling to study both anatomy and functions of the islet.
Published: 2017

21. Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.

Author: Beatrice Cousin, Emmanuel Ravet, Sandrine Poglio, Fabienne De Toni, Mélanie Bertuzzi, Hubert Lulka, Ismahane Touil, Mireille André, Jean-Louis Grolleau, Jean-Marie Péron, Jean-Pierre Chavoin, Philippe Bourin, Luc Pénicaud, Louis Casteilla, Louis Buscail, and Pierre Cordelier
Subjects: Medicine, Science
Abstract: BackgroundNormal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aberrant stromal-epithelial interactions contribute to pancreatic ductal adenocarcinoma (PDAC) spread and metastasis, and this raises the possibility that novel stroma-targeted therapies represent additional approaches for combating this malignant disease. The aim of the present study was to determine the effect of human stromal cells derived from adipose tissue (ADSC) on pancreatic tumor cell proliferation.Principal findingsCo-culturing pancreatic tumor cells with ADSC and ADSC-conditioned medium sampled from different donors inhibited cancer cell viability and proliferation. ADSC-mediated inhibitory effect was further extended to other epithelial cancer-derived cell lines (liver, colon, prostate). ADSC conditioned medium induced cancer cell necrosis following G1-phase arrest, without evidence of apoptosis. In vivo, a single intra-tumoral injection of ADSC in a model of pancreatic adenocarcinoma induced a strong and long-lasting inhibition of tumor growth.ConclusionThese data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available.
Published: 2009
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22. Taste Perception and Cerebral Activity in the Human Gustatory Cortex Induced by Glucose, Fructose, and Sucrose Solutions

Author: Laurent Brondel, Lucie Janin, Corinne Leloup, Luc Pénicaud, Agnès Jacquin-Piques, Thomas Mouillot, Sophie Barthet, Marie-Claude Brindisi, Camille Creteau, Hervé Devilliers, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne et maladies systémiques (SOC 2) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), and Service de Neurophysiologie Clinique (CHU Dijon)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Taste, Sucrose, Molar concentration, Physiology, [SDV]Life Sciences [q-bio], media_common.quotation_subject, gustatory evoked potentials, Fructose, 03 medical and health sciences, Behavioral Neuroscience, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Taste receptor, Physiology (medical), Perception, Internal medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Humans, media_common, Cerebral Cortex, Taste Perception, Sweetness, Sensory Systems, Solutions, 030104 developmental biology, Endocrinology, Glucose, chemistry, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Gustatory cortex, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Glucose, fructose, and sucrose are important carbohydrates in Western diets with particular sweetness intensity and metabolisms. No study has compared their cerebral detection and their taste perception. Gustatory evoked potentials (GEPs), taste detection thresholds, intensity perception, and pleasantness were compared in response to glucose, fructose, and sucrose solutions at similar sweetness intensities and at identical molar concentrations. Twenty-three healthy subjects were randomly stimulated with 3 solutions of similar sweetness intensity (0.75 M of glucose, 0.47 M of fructose and 0.29 M of sucrose – sit. A), and with an identical molar concentration (0.29 M – sit. B). GEPs were recorded at gustatory cortex areas. Intensity perception and hedonic values of each solution were evaluated as were gustatory thresholds of the solutions. No significant difference was observed concerning the GEP characteristics of the solutions according to their sweetness intensities (sit. A) or their molar concentration (sit. B). In sit. A, the 3 solutions were perceived to have similar intensities and induced similar hedonic sensations. In sit. B, the glucose solution was perceived to be less intense and pleasant than the fructose and the sucrose solutions (P < 0.001) and the fructose solution was perceived to be less intense and pleasant than the sucrose (P < 0.001). Since GEP recordings were similar for glucose, fructose, and sucrose solutions whatever the concentrations, activation of same taste receptor induces similar cortical activation, even when the solutions were perceived differently. Sweet taste perception seems to be encoded by a complex chemical cerebral neuronal network.
Published: 2019

23. Metformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids

Author: Xavier Fioramonti, Siriporn C. Chattipakorn, Stella Manta, Sophie Layé, Hugo Martin, Marie Adeline Marques, Fabien Ducrocq, Sébastien Bullich, Juliane Costa Silva Zemdegs, Luc Pénicaud, Hiranya Pintana, Nipon Chattipakorn, Bruno P. Guiard, Claire Rampon, Cedric Moro, UFR Pharmacie - Université Paris-Sud, Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), EA 3544, Université Paris-Sud - Paris 11 (UP11), Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), UMR 1286-NutriNeuro Nutrition et Neurobiologie intégrée, Institut National de la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, medicine.drug_class, hippocampus, [SDV]Life Sciences [q-bio], Type 2 diabetes, Anxiety, Serotonergic, Anxiolytic, 03 medical and health sciences, Mice, 0302 clinical medicine, Insulin resistance, Internal medicine, insulin resistance, medicine, Animals, Hypoglycemic Agents, branched-chain amino acids, Research Articles, ComputingMilieux_MISCELLANEOUS, Fluoxetine, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, General Neuroscience, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Antidepressive Agents, 3. Good health, Metformin, serotonin, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Anti-Anxiety Agents, depression, Antidepressant, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Serotonin, business, metformin, 030217 neurology & neurosurgery, Amino Acids, Branched-Chain, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Epidemiological studies indicate that insulin resistance (IR), a hallmark of type 2 diabetes, is associated with an increased risk of major depression. Here, we demonstrated that male mice fed a high-fat diet (HFD) exhibited peripheral metabolic impairments reminiscent of IR accompanied by elevated circulating levels of branched-chain amino acids (BCAAs), whereas both parameters were normalized by chronic treatment with metformin (Met). Given the role of BCAAs in the regulation of tryptophan influx into the brain, we then explored the activity of the serotonin (5-HT) system. Our results indicated that HFD-fed mice displayed impairment in the electrical activity of dorsal raphe 5-HT neurons, attenuated hippocampal extracellular 5-HT concentrations and anxiety, one of the most visible and early symptoms of depression. On the contrary, Met stimulated 5-HT neurons excitability and 5-HT neurotransmission while hindering HFD-induced anxiety. Met also promoted antidepressant-like activities as observed with fluoxetine. In light of these data, we designed a modified HFD in which BCAA dietary supply was reduced by half. Deficiency in BCAAs failed to reverse HFD-induced metabolic impairments while producing antidepressant-like activity and enhancing the behavioral response to fluoxetine. Our results suggest that Met may act by decreasing circulating BCAAs levels to favor serotonergic neurotransmission in the hippocampus and promote antidepressant-like effects in mice fed an HFD. These findings also lead us to envision that a diet poor in BCAAs, provided either alone or as add-on therapy to conventional antidepressant drugs, could help to relieve depressive symptoms in patients with metabolic comorbidities. SIGNIFICANCE STATEMENT Insulin resistance in humans is associated with increased risk of anxiodepressive disorders. Such a relationship has been also found in rodents fed a high-fat diet (HFD). To determine whether insulin-sensitizing strategies induce anxiolytic- and/or antidepressant-like activities and to investigate the underlying mechanisms, we tested the effects of metformin, an oral antidiabetic drug, in mice fed an HFD. Metformin reduced levels of circulating branched-chain amino acids, which regulate tryptophan uptake within the brain. Moreover, metformin increased hippocampal serotonergic neurotransmission while promoting anxiolytic- and antidepressant-like effects. Moreover, a diet poor in these amino acids produced similar beneficial behavioral property. Collectively, these results suggest that metformin could be used as add-on therapy to a conventional antidepressant for the comorbidity between metabolic and mental disorders.
Published: 2019

24. Proof of concept: Effect of GLP-1 agonist on food hedonic responses and taste sensitivity in poor controlled type 2 diabetic patients

Author: Sophie Barthet, Marie-Claude Brindisi, Luc Pénicaud, Bruno Vergès, Sylvie Grall, Corinne Leloup, Claire Fenech, Pascal Schlich, Karine Astruc, Thomas Mouillot, Sophie Meillon, Laurent Brondel, Agnès Jacquin-Piques, Fabienne Liénard, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Grant from the Region of Burgundy, France (PARI 2014)., Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Taste, Hunger, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Fatty foods, Type 2 diabetes, 030204 cardiovascular system & hematology, Choice Behavior, Eating, 0302 clinical medicine, Weight loss, Glucagon-Like Peptide 1, food behavior, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Aged, 80 and over, diabetes, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, digestive, oral, and skin physiology, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Prognosis, 3. Good health, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, medicine.symptom, medicine.drug, Clinical psychology, Adult, Adolescent, 030209 endocrinology & metabolism, 03 medical and health sciences, Food Preferences, Young Adult, Diabetes mellitus, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Obesity, Aged, Liraglutide, business.industry, Glp 1 agonist, nutritional and metabolic diseases, Feeding Behavior, medicine.disease, Diabetes Mellitus, Type 2, GLP1-analogue, Mental Recall, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, taste perception, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers, Follow-Up Studies
Abstract: International audience; AIMS: GLP-1 analogues decrease food intake and have great promise for the fight against obesity. Little is known about their effects on food hedonic sensations and taste perception in poor controlled patients with type 2 diabetes (T2D). MATERIALS AND METHODS: Eighteen T2D patients with BMI >/=25kg/m(2) and poor controlled glycemia were studied before and after 3 months of treatment with Liraglutide. Detection thresholds for salty, sweet and bitter tastes, optimal preferences, olfactory liking, wanting and recalled liking for several food items were assessed. Subjects also answered questionnaires to measure their attitudes to food. RESULTS: T2D patients had a significant decrease in bodyweight and HbA1c after treatment with Liraglutide. Liraglutide improved gustative detection threshold of sweet flavors, and decreased wanting for sweet foods and recalled liking for fatty foods. It also led to a decrease in feelings of hunger. CONCLUSIONS: Liraglutide increases sensitivity to sweet tastes and decreases pleasure responses for fatty foods in poor controlled T2D patients, and is of particular interest in the understanding of the mechanisms of weight loss. CLINICAL TRIAL: NCT02674893.
Published: 2019

25. The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system

Author: Luc Pénicaud, Demetra Rodaros, Khalil Bouyakdan, Bouchra Taïb, Hugo Martin, Eric Biron, Xavier Fioramonti, Lionel Budry, Daniela Cota, Thierry Alquier, F. Liénard, Chloé Chrétien, Zoé Husson, Stephanie Fulton, Laboratory of Molecular Genetics [Montréal, Canada], Institut De Recherches Cliniques De Montreal - IRCM [Canada], Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Laboratory of Molecular Genetics, Institut de recherches cliniques de Montréal, Centre de recherche du Chum [Montréal] (CRCHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université Laval, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), CRCHUM, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Université Laval [Québec] (ULaval), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Grants from the Canadian Institutes of Health Research (MOP115042 and PJT153035 to TA), Marie Curie Foundation (CIG NeuROSenS PCIG09-GA-2011-293738 to XF), Société Francophone du Diabète and Diabète Québec (to TA) and Réseau cardiométabolique, diabète & obésité from Fonds de Recherche Québec-Santé (CMDO-FRQS to TA and XF) and from INSERM, Agence Nationale Recherche ANR-13-BSV4-0006, ANR-18-CE14-0029-02 (to DC) and ANR-10-LABX-43 Labex BRAIN (to DC and XF). HM and CC were supported by a fellowship from the department AlimH INRA and the Région Nouvelle Aquitaine or Région Bourgogne, respectively. XF and LP were also supported by the PARI Région Bourgogne. TA, SF and EB were supported by a salary award from FRQS. KB and BT were supported by a fellowship from Diabète Québec and LB by a fellowship from Diabetes Canada., and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Pro-Opiomelanocortin, Gliotransmitter, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hyperphagia, Energy homeostasis, Cell Line, neuroscience, 03 medical and health sciences, Eating, Mice, 0302 clinical medicine, Proopiomelanocortin, Central melanocortin system, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Obesity, ComputingMilieux_MISCELLANEOUS, Diazepam Binding Inhibitor, Mice, Knockout, Neurons, Arc (protein), biology, Chemistry, GABAA receptor, General Medicine, Viral rescue, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Cell biology, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Astrocytes, biology.protein, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Melanocortin, Energy Metabolism, metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: International audience; Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-lineage neural cells, promoted diet-induced hyperphagia and obesity in both male and female mice, an effect prevented by viral rescue of ACBP in ARC astrocytes. ACBP-astrocytes were observed in apposition with proopiomelanocortin (POMC) neurons and ODN selectively activated POMC neurons through the ODN-GPCR but not GABAA, and supressed feeding while increasing carbohydrate utilization via the melanocortin system. Similarly, ACBP overexpression in ARC astrocytes reduced feeding and weight gain. Finally, the ODN-GPCR agonist decreased feeding and promoted weight loss in ob/ob mice. These findings uncover ACBP as an ARC gliopeptide playing a key role in energy balance control and exerting strong anorectic effects via the central melanocortin system.
Published: 2019

26. Mitochondria in Obesity and Type 2 Diabetes: Concluding Review and Research Perspectives

Author: Michel Rigoulet, Luc Pénicaud, Béatrice Morio, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Aviesan, Centre National de la Recherche Scientifique (CNRS), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Morio, B. and Penicaud, L. and Rigoulet, M., Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Bordeaux (UB), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), CarMeN, laboratoire, and Morio, B. and Penicaud, L. and Rigoulet, M.
Subjects: Food intake, binding, nadh, [SDV]Life Sciences [q-bio], Type 2 diabetes, Mitochondrion, Biology, yeast, 03 medical and health sciences, cytochrome-c-oxidase, supercomplexes, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, calcium homeostasis, 030302 biochemistry & molecular biology, respiratory-chain, dynamics, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Obesity, 3. Good health, [SDV] Life Sciences [q-bio], Energy expenditure, membranes, Adaptation, Neuroscience, Whole Organism, complex
Abstract: International audience; Obesity and type 2 diabetes (T2DM) are metabolic disorders that have emerged as two of the most serious health issues in the world. Both are related to chronic inequality between food intake and energy expenditure, giving rise to energy imbalance over long-term periods of time. This imbalance has major consequences on the metabolic fluxes in the different tissues or organs and at the whole organism level. Within the cell, mitochondria are at the front line to initiate adaptation to these changes and, therefore, are the primary targets affected. Mitochondria are key organelles in which fuel substrates are oxidized to produce ATP from cascades of redox reactions. An important notion to understand the etiology of metabolic diseases, however, is that in all tissues and organs, energy and redox processes are closely interlinked within the mitochondria and govern major cell metabolic adaptations. This chapter is not a summary of the previous ones but has two objectives: to emphasize notions that, in the opinion of the three of us, appear to be most important, and to propose some directions for future research.
Published: 2019

27. Factors influencing the membrane fluidity and the impact on production of lactic acid bacteria starters

Author: Stéphanie Passot, E. Elizabeth Tymczyszyn, Andrea Gómez-Zavaglia, Caroline Pénicaud, Fernanda Fonseca, Génie et Microbiologie des Procédés Alimentaires (GMPA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Departamento de Ciencia y Tecnología [Buenos Aires], Universidad Nacional de Quilmes (UNQ), Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Comisión de Investigaciones Científicas [Buenos Aires] (CIC)-Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP), European Project: 777657,H2020-EU.1.3.3. - Stimulating innovation by means of cross-fertilisation of knowledge,777657,MSCA-RISE(2018), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP)-Comisión de Investigaciones Científicas [Buenos Aires] (CIC), AgroParisTech-Institut National de la Recherche Agronomique (INRA), and 777657European Union's Horizon 2020 Marie Sklodowska-Curie research and innovation program
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Otras Ingenierías y Tecnologías, Membrane Fluidity, [SDV]Life Sciences [q-bio], Cell, Preservation, Biological, Fluorescence Polarization, Oxidative phosphorylation, INGENIERÍAS Y TECNOLOGÍAS, Environmental stress, Applied Microbiology and Biotechnology, Phase Transition, Alimentos y Bebidas, 03 medical and health sciences, chemistry.chemical_compound, Membrane Lipids, Lactobacillales, Stress, Physiological, Membrane fluidity, medicine, PRESERVATION PROCESSES, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Food science, Lipid bilayer phase behavior, Lipid phase transition, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Chemistry, Cell Membrane, General Medicine, LIPID PHASE TRANSITION, Química, ENVIRONMENTAL STRESS, Preservation processes, biology.organism_classification, Lactic acid, Membrane, medicine.anatomical_structure, 13. Climate action, Fermentation, FLUORESCENCE ANISOTROPY, Bacteria, Biotechnology, Fluorescence anisotropy
Abstract: Production of lactic acid bacteria starters for manufacturing food, probiotic, and chemical products requires the application of successive steps: fermentation, concentration, stabilization, and storage. Despite process optimization, losses of bacterial viability and functional activities are observed after stabilization and storage steps due to cell exposure to environmental stresses (thermal, osmotic, mechanical, and oxidative). Bacterial membrane is the primary target for injury and its damage is highly dependent on its physical properties and lipid organization. Membrane fluidity is a key property for maintaining cell functionality, and depends on lipid composition and cell environment. Extensive evidence has been reported on changes in membrane fatty acyl chains when modifying fermentation conditions. However, a deep characterization of membrane physical properties and their evolution following production processes is scarcely reported. Therefore, the aims of this mini-review are (i) to define the membrane fluidity and the methods used to assess it and (ii) to summarize the effect of environmental conditions on membrane fluidity and the resulting impact on the resistance of lactic acid bacteria to the stabilization processes. This will make it possible to highlight existing gaps of knowledge and opens up novel approaches for future investigations., Centro de Investigación y Desarrollo en Criotecnología de Alimentos
Published: 2019

28. Lack of Hypothalamus Polysialylation Inducibility Correlates With Maladaptive Eating Behaviors and Predisposition to Obesity

Author: Selma Ben Fradj, Amélie Laderrière, Veronique Douard, Caroline Rigault, Gaëlle Boudry, Danae Nuzzaci, Luc Pénicaud, Alexandre Benani, Emmanuelle Nédélec, Aleth Lemoine, Fabienne Liénard, Xavier Brenachot, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, CNRS, INRA (Action prioritaire BiotaBrain), Region Bourgogne-Franche Comte (PARI), Region Bourgogne-Franche Comte (FEDER-FSE Bourgogne 2014-2020), ANR [ANR-13-JSV1-0003-01], Benani, Alexandre, Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: 0301 basic medicine, obesity, food intake, PSA-NCAM, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, brain, maladaptive eating behavior, lcsh:TX341-641, Biology, Overweight, Energy homeostasis, 03 medical and health sciences, Neuroplasticity, medicine, Food and Nutrition, hypothalamus, media_common, Nutrition, Original Research, Nutrition and Dietetics, synaptic plasticity, comportement alimentaire, polysialylation, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neurosciences, Appetite, medicine.disease, prise alimentaire, Obesity, 3. Good health, [SDV] Life Sciences [q-bio], Eating disorders, obésité, 030104 developmental biology, nervous system, Hypothalamus, Neurons and Cognition, Synaptic plasticity, Alimentation et Nutrition, plasticité synaptique, cerveau, medicine.symptom, lcsh:Nutrition. Foods and food supply, Neuroscience, Food Science
Abstract: This original research article (6 p.) is part of the research topic . Specialty section: This article was submitted to Neuroenergetics, Nutrition and Brain Health, a section of the journal Frontiers in Nutrition.; International audience; High variability exists in individual susceptibility to develop overweight in an obesogenic environment and the biological underpinnings of this heterogeneity are poorly understood. In this brief report, we show in mice that the vulnerability to diet-induced obesity is associated with low level of polysialic acid-neural cell adhesion molecule (PSA-NCAM), a factor of neural plasticity, in the hypothalamus. As we previously shown that reduction of hypothalamic PSA-NCAM is sufficient to alter energy homeostasis and promote fat storage under hypercaloric pressure, inter-individual variability in hypothalamic PSA-NCAM might account for the vulnerability to diet-induced obesity. These data support the concept that reduced plasticity in brain circuits that control appetite, metabolism and body weight confers risk for eating disorders and obesity.
Published: 2018

29. High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice

Author: Juliane Costa Silva Zemdegs, Xavier Fioramonti, Bruno P. Guiard, Luc Pénicaud, Gaël Quesseveur, and David Jarriault
Subjects: 0301 basic medicine, Pharmacology, medicine.medical_specialty, Microdialysis, nutritional and metabolic diseases, medicine.disease, 3. Good health, Impaired glucose tolerance, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Endocrinology, Insulin resistance, Diabetes mellitus, Internal medicine, medicine, Escitalopram, Antidepressant, Major depressive disorder, Psychology, Reuptake inhibitor, 030217 neurology & neurosurgery, medicine.drug
Abstract: BACKGROUND AND PURPOSE The link between type 2 diabetes mellitus (T2DM) and depression is bidirectional. However, the possibility that metabolic disorders may elicit anxiogenic-like/depressive-like symptoms or alter the efficacy of antidepressant drugs remains poorly documented. This study explored the influence of T2DM on emotionality and proposed a therapeutic strategy that might be used in depressed diabetic patients. EXPERIMENTAL APPROACH Mice were fed a high-fat diet (HFD) and subjected to a full comprehensive metabolic and behavioural analysis to establish correlations between metabolic and psychiatric disorders. In vivo intra-hippocampal microdialysis was also applied to propose a mechanism underpinning the phenotype of mice fed the HFD. Finally, we tested whether chronic administration of the selective 5-HT reuptake inhibitor escitalopram or HFD withdrawal could reverse HFD-induced metabolic and behavioural anomalies. KEY RESULTS The increased body weight, hyperglycaemia and impaired glucose tolerance in response to HFD were correlated with anxiogenic-like/depressive-like symptoms. Moreover, this phenotype was associated with decreased extracellular 5-HT levels in the hippocampus which may result from increased sensitivity of the dorsal raphe 5-HT1A autoreceptor. Interestingly, the beneficial effect of prolonged administration of escitalopram was abolished in HFD-fed mice. On the contrary, HFD withdrawal completely reversed metabolic impairments and positively changed symptoms of anxiety, although some behavioural anomalies persisted. CONCLUSIONS AND IMPLICATIONS Our data provide clear-cut evidence that both pathologies are finely correlated and associated with impaired 5-HT mediated neurotransmission in the hippocampus. Further experiments are warranted to define the most adequate strategy for the treatment of such co-morbidity.
Published: 2015

30. Sensory functions and Alzheimer's disease: a multi-disciplinary approach

Author: Thierry Pozzo, Fabrice Gzil, Paul-Ariel Kenigsberg, Christophe Reintjens, Philippe Robert, Gérard Brand, Muriel Boucart, Arach Madjlessi, Évelyne Malaquin-Pavan, Alain Berard, Didier Bouccara, Eric Salmon, Kevin Charras, Luis Garcia-Larrea, Laurent Vergnon, Pierre Krolak-Salmon, Hervé Platel, Luc Pénicaud, and Jean-Pierre Aquino
Subjects: Male, Sensation, Poison control, Context (language use), Sensory system, 03 medical and health sciences, Cognition, 0302 clinical medicine, Quality of life (healthcare), Alzheimer Disease, Motor cognition, Humans, Medicine, Dementia, Cognitive rehabilitation therapy, 030223 otorhinolaryngology, Biological Psychiatry, Aged, Aged, 80 and over, business.industry, Pain Perception, medicine.disease, 3. Good health, Neuropsychology and Physiological Psychology, Female, Neurology (clinical), Geriatrics and Gerontology, business, Neuroscience, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: Relations between sensory functions and Alzheimer's disease are still under-explored. To understand them better, the Fondation Médéric Alzheimer has brought together a multi-disciplinary expert group. Aristote's five senses must be enhanced by today's knowledge of proprioception, motor cognition and pain perception. When cognition breaks down, the person with dementia perceives the world around her with her sensory experience, yet is unable to integrate all this information to understand the context. The treatment of multiple sensory inputs by the brain is closely linked to cognitive processes. Sensory deficits reduce considerably the autonomy of people with dementia in their daily life and their relations with others, increase their social isolation and the risk of accidents. Professionals involved with neurodegenerative diseases remain poorly aware of sensory deficits, which can bias the results of cognitive tests. However, there are simple tools to detect these deficits, notably for vision, hearing and balance disorders, which can be corrected. Many interventions for cognitive rehabilitation or quality of life improvement are based on sensory functions. The environment of people with dementia must be adapted to become understandable, comfortable, safe and eventually therapeutic.
Published: 2015

31. FP780FOOD PREFERENCES MODIFIED BY THE HEMODIALYSIS SESSION: SHOULD WE ADAPT DIETETIC ADVICES?

Author: Christiane Mousson, Luc Pénicaud, Laurent Brondel, Sophie Meillon, and Anna Filancia
Subjects: Transplantation, medicine.medical_specialty, business.industry, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Physical therapy, Medicine, Medical emergency, Session (computer science), Hemodialysis, business
Published: 2015

32. Understanding the responses of Saccharomyces cerevisiae yeast strain during dehydration processes using synchrotron infrared spectroscopy

Author: Stéphanie Passot, Fernanda Fonseca, Thi Xuan Sam Nguyen, Rémi Saurel, Stéphane Guyot, Florence Husson, Christophe Sandt, Caroline Pénicaud, Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Procédés Microbiologiques et Biotechnologiques (PMB), Procédés Alimentaires et Microbiologiques (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Génie et Microbiologie des Procédés Alimentaires (GMPA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris-Saclay, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Physico-Chimie de l'Aliment et du Vin (PCAV), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, SMIS beamline [20140185], Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Procédés Alimentaires et Microbiologiques [Dijon] ( PAM ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté ( UBFC ), Génie et Microbiologie des Procédés Alimentaires ( GMPA ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Synchrotron SOLEIL ( SSOLEIL ), and Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, Spectrophotometry, Infrared, Saccharomyces cerevisiae, Infrared spectroscopy, 01 natural sciences, Biochemistry, Analytical Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Protein structure, Lipid oxidation, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Electrochemistry, medicine, Environmental Chemistry, Relative humidity, Dehydration, Spectroscopy, biology, Chemistry, 010401 analytical chemistry, [ SDV.IDA ] Life Sciences [q-bio]/Food engineering, food and beverages, Glutathione, medicine.disease, biology.organism_classification, Yeast, Culture Media, 0104 chemical sciences, 030104 developmental biology, Synchrotrons
Abstract: International audience; For the first time, synchrotron infrared spectroscopy was performed on yeast during dehydration processes in real time with simultaneously controlled relative humidity and temperature. This led us to investigate the biochemical modification in relation to the dehydration of Saccharomyces cerevisiae. The correlation between the hydration level and yeast survival was observed. Following the test conditions, the modification of the protein structure was observed. However, no evident modification of the lipid composition resulting from dehydration was observed. Furthermore, the results showed that the medium rich in nutrients and glutathione precursors can improve yeast survival during dehydration at 45 °C. This could be related to the high relative amounts of CH3 groups in the lipid composition assigned to the low lipid oxidation level in this case. Our work demonstrated the feasibility of using S-FTIR for investigating yeast responses to dehydration processes in real time. This method can be used for understanding the effect of dehydration/rehydration on the biochemical modification of yeast.
Published: 2017

33. Physiology and biochemistry of type 2 diabetes: A tribute to Dr Alain Ktorza

Author: Luc Pénicaud, Christophe Magnan, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, Philosophy, [SDV]Life Sciences [q-bio], 030302 biochemistry & molecular biology, Tribute, Physiology, General Medicine, Type 2 diabetes, medicine.disease, Biochemistry, 03 medical and health sciences, medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2017

34. Hypothalamic Apelin/Reactive Oxygen Species Signaling Controls Hepatic Glucose Metabolism in the Onset of Diabetes

Author: Anne Drougard, Claude Knauf, Jean Lesage, Alexandre Benani, Lionel Carneiro, Philippe Valet, Patrice D. Cani, Lucie Geurts, Anne-Catherine Prats, Didier Vieau, Audren Fournel, Xavier Brenachot, Thomas Cadoudal, Corinne Leloup, Luc Pénicaud, Alexandra Gouazé, Thibaut Duparc, Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université de Bourgogne (UB), Catholic Univ Louvain, LDRI, Metab & Nutr Res Grp, B-1200 Brussels, Belgium, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Contrôle de la Traduction et Thérapie Génique des Pathologies Vasculaires (TRADGENE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Environnement périnatal et croissance - EA 4489 (EPS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Univ Toulouse, UPS, TRADGENE, Toulouse, France, Environnement périnatal et croissance, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Fac Med Toulouse, INSERM, F-31073 Toulouse, France, Univ Toulouse 3, UPS, I2MC, F-31062 Toulouse, France, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Université de Bourgogne ( UB ), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille )
Subjects: Blood Glucose, Male, Sympathetic nervous system, LIVER, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Glycogenolysis, Physiology, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Clinical Biochemistry, Mice, Obese, Biochemistry, SYMPATHETIC-NERVE ACTIVITY, APELIN, BRAIN, General Environmental Science, INSULIN-RESISTANCE, 3. Good health, Apelin, Original Research Communications, ADIPOSE-TISSUE, medicine.anatomical_structure, Intercellular Signaling Peptides and Proteins, Signal Transduction, EXPRESSION, medicine.medical_specialty, Hypothalamus, Biology, Carbohydrate metabolism, Autonomic Nervous System, Insulin resistance, Adipokines, Internal medicine, Diabetes mellitus, medicine, Animals, Molecular Biology, Gluconeogenesis, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, Cell Biology, medicine.disease, Mice, Inbred C57BL, MICE, Glucose, Endocrinology, Diabetes Mellitus, Type 2, RAT, General Earth and Planetary Sciences, Liver function, Reactive Oxygen Species, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, SYSTEM
Abstract: Aims: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver glucose metabolism and glycemia. Results: We show that icv apelin injection stimulates liver glycogenolysis and gluconeogenesis via an over-activation of the sympathetic nervous system (SNS), leading to fasted hyperglycemia. The effect of central apelin on liver function is dependent of an increased production of hypothalamic reactive oxygen species (ROS). These data are strengthened by experiments using lentiviral vector-mediated over-expression of apelin in hypothalamus of mice that present over-activation of SNS associated to an increase in hepatic glucose production. Finally, we report that mice fed a high-fat diet present major alterations of hypothalamic apelin/ROS signaling, leading to activation of glycogenolysis. Innovation/Conclusion: These data bring compelling evidence that hypothalamic apelin is one master switch that participates in the onset of diabetes by directly acting on liver function. Our data support the idea that hypothalamic apelin is a new potential therapeutic target to treat diabetes. Antioxid. Redox Signal. 20, 557–573.
Published: 2014

35. Hypothalamic Astroglial Connexins are Required for Brain Glucose Sensing-Induced Insulin Secretion

Author: Xavier Fioramonti, Brandon H. Cline, Chloé Chrétien, Christian Giaume, Fawzia Baba-Aissa, Luc Pénicaud, Sylvie Grall, Lionel Carneiro, Camille Allard, Corinne Leloup, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Collège de France (CdF), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), and Collège de France ( CdF )
Subjects: Male, INVOLVEMENT, HOMEOSTASIS, medicine.medical_specialty, medicine.medical_treatment, Nerve Tissue Proteins, Carbohydrate metabolism, Biology, ASTROCYTES, Connexins, connexin 43, RATS, astrocyte, Internal medicine, Insulin Secretion, medicine, Animals, Insulin, TANYCYTES, Rats, Wistar, hypothalamus, IN-VIVO, HEMICHANNELS, glucose sensing, ARCUATE NUCLEUS, Gap junction, Fasting, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, BARRIER, connexin 30, NETWORKS, Glucose, Endocrinology, medicine.anatomical_structure, Neurology, Hypothalamus, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], RNA Interference, Original Article, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], sense organs, Neurology (clinical), Cardiology and Cardiovascular Medicine, Thermogenesis, Intracellular, Homeostasis, Astrocyte
Abstract: Supplementary Information accompanies the paper on the Journal of Cerebral Blood Flow & Metabolism website; Hypothalamic glucose detection participates in maintaining glycemic balance, food intake, and thermogenesis. Although hypothalamic neurons are the executive cells involved in these responses, there is increasing evidence that astrocytes participate in glucose sensing (GS); however, it is unknown whether astroglial networking is required for glucose sensitivity. Astroglial connexins 30 and 43 (Cx30 and Cx43) form hexameric channels, which are apposed in gap junctions, allowing for the intercellular transfer of small molecules such as glucose throughout the astroglial networks. Here, we hypothesized that hypothalamic glucose sensitivity requires these connexins. First, we showed that both Cxs are enriched in the rat hypothalamus, with highly concentrated Cx43 expression around blood vessels of the mediobasal hypothalamus (MBH). Both fasting and high glycemic levels rapidly altered the protein levels of MBH astroglial connexins, suggesting cross talk within the MBH between glycemic status and the connexins' ability to dispatch glucose. Finally, the inhibition of MBH Cx43 (by transient RNA interference) attenuated hypothalamic glucose sensitivity in rats, which was demonstrated by a pronounced decreased insulin secretion in response to a brain glucose challenge. These results illustrate that astroglial connexins contribute to hypothalamic GS.
Published: 2013

36. Structural brain changes linked to delayed first language acquisition in congenitally deaf individuals

Author: Pamela Witcher, Krista L. Hyde, Denise Klein, Sidonie Pénicaud, Jen-Kai Chen, Robert J. Zatorre, and Rachel I. Mayberry
Subjects: Adult, Male, medicine.medical_specialty, American Sign Language, Cognitive Neuroscience, First language, Deafness, Sign language, Audiology, Language Development, 050105 experimental psychology, White matter, Sign Language, 03 medical and health sciences, 0302 clinical medicine, Neuroplasticity, Image Processing, Computer-Assisted, medicine, Humans, 0501 psychology and cognitive sciences, medicine.diagnostic_test, 05 social sciences, Age Factors, Brain, Middle Aged, language.human_language, First language acquisition, medicine.anatomical_structure, Age of Acquisition, Neurology, language, Female, Functional magnetic resonance imaging, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: Early language experience is essential for the development of a high level of linguistic proficiency in adulthood and in a recent functional Magnetic Resonance Imaging (fMRI) experiment, we showed that a delayed acquisition of a first language results in changes in the functional organization of the adult brain (Mayberry et al., 2011). The present study extends the question to explore if delayed acquisition of a first language also modulates the structural development of the brain. To this end, we carried out anatomical MRI in the same group of congenitally deaf individuals who varied in the age of acquisition of a first language, American Sign Language -ASL (Mayberry et al., 2011) and used a neuroanatomical technique, Voxel-Based Morphometry (VBM), to explore changes in gray and white matter concentrations across the brain related to the age of first language acquisition. The results show that delayed acquisition of a first language is associated with changes in tissue concentration in the occipital cortex close to the area that has been found to show functional recruitment during language processing in these deaf individuals with a late age of acquisition. These findings suggest that a lack of early language experience affects not only the functional but also the anatomical organization of the brain.
Published: 2013

37. Gut commensal E. coli proteins activate host satiety pathways following nutrient-induced bacterial growth

Author: Fabienne Liénard, Naouel Tennoune, Jean-Claude do Rego, Xavier Fioramonti, Luc Pénicaud, Nicolas Lucas, Martine Pestel-Caron, Tomas Hökfelt, David Vaudry, Pierre Déchelotte, Charlène Guérin, Justine Jacquemot, Marie François, Johann Peltier, Jonathan Breton, Ivor S. Ebenezer, Sergueï O. Fetissov, Romain Legrand, Philippe Chan, Alexis Goichon, Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU), Hôpital Charles Nicolle [Tunis], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), University of Portsmouth, Karolinska Institutet [Stockholm], EU INTERREG IVA 2 Seas Program 7-003-FR_TC2N Haute-Normandie Region, France Marie Curie CIG NeuROSens, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Institute for Research and Innovation in Biomedicine ( IRIB ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau ( ADEN ), Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes ( GRAM 1.0 ), Normandie Université ( NU ) -Normandie Université ( NU ), Normandie Université ( NU ), CHU Charles Nicolle, CHU Rouen, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Plate-forme de Protéomique PISSARO, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Service Commun d'Analyse Comportementale (SCAC), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de nutrition [CHU Rouen], and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
Subjects: Male, Proteomics, 0301 basic medicine, intestinal microbiota, Pro-Opiomelanocortin, Physiology, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Pharmacy, Bacterial growth, Gut flora, medicine.disease_cause, Satiety Response, in-vivo, Energy homeostasis, Rats, Sprague-Dawley, Mice, neuropeptide-y, Adenosine Triphosphate, Glucagon-Like Peptide 1, arcuate nucleus, high-fat, Heat-Shock Proteins, media_common, Neurons, 2. Zero hunger, biology, Escherichia coli Proteins, digestive, oral, and skin physiology, Endopeptidase Clp, food-intake, Amygdala, Glucagon-like peptide-1, Cell biology, Biochemistry, Proteome, Female, Proto-Oncogene Proteins c-fos, media_common.quotation_subject, Hypothalamus, 03 medical and health sciences, Escherichia coli, medicine, Animals, Peptide YY, Rats, Wistar, Molecular Biology, energy homeostasis, melanocortin-4 receptor, Appetite, Feeding Behavior, Cell Biology, biology.organism_classification, Electrophysiological Phenomena, Gastrointestinal Tract, Mice, Inbred C57BL, 030104 developmental biology, glucagon-like peptide-1, escherichia-coli, CLPB, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; The composition of gut microbiota has been associated with host metabolic phenotypes, but it is not known if gut bacteria may influence host appetite. Here we show that regular nutrient provision stabilizes exponential growth of E. coli, with the stationary phase occurring 20 min after nutrient supply accompanied by bacterial proteome changes, suggesting involvement of bacterial proteins in host satiety. Indeed, intestinal infusions of E. coli stationary phase proteins increased plasma PYY and their intraperitoneal injections suppressed acutely food intake and activated c-Fos in hypothalamic POMC neurons, while their repeated administrations reduced meal size. ClpB, a bacterial protein mimetic of alpha-MSH, was upregulated in the E. coli stationary phase, was detected in plasma proportional to ClpB DNA in feces, and stimulated firing rate of hypothalamic POMC neurons. Thus, these data show that bacterial proteins produced after nutrient-induced E. coli growth may signal meal termination. Furthermore, continuous exposure to E. coli proteins may influence long-term meal pattern.
Published: 2016

38. Taste disorders in disease

Author: Thomas Mouillot, Agnès Jacquin-Piques, Luc Pénicaud, Marie-Claude Brindisi, Laurent Brondel, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC), Hepato-Gastro-Enterology, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Endocrinology, Neurology, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Université Bourgogne Franche-Comté ( UBFC ), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )
Subjects: Taste, business.industry, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, media_common.quotation_subject, Gastronomy, Sensory system, Appetite, Disease, Olfaction, medicine.disease, Malnutrition, Taste disorder, Medicine, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Neuroscience, media_common
Abstract: Among the different sensory systems, gustation is one of the most elaborate. In its sensory task, gustation is helped by interactions with other sensory systems (olfaction, vision, audition, and somatosensory, trigeminal and thermal sensations). It allows the detection and identification of soluble compounds which can be ingested or must be avoided. This function is fundamental to ingestive behavior (energy intake and selection of nutrients) in order to meet physiological needs. Taste is also fundamental to the genesis of hedonic sensations and, therefore, the desire to eat (appetite). The tasting step is also the first stage of the digestion, absorption, and storage of nutrients due to anticipatory reflexes. Taste disorders are, therefore, not simple hedonic alterations of the epicurean canon of gastronomy; taste disorders can worsen and even compromise vital functions (malnutrition and aggravation of an underlying disease), and they always reduce quality of life. Many drugs and numerous diseases can cause gustatory loss. The mechanisms leading to taste alteration are varied. In medical practice, taste problems are frequent but not diagnosed often enough, in particular in metabolic syndrome and obesity, in neurodegenerative diseases, and in cancer. Increasing knowledge of taste disorders in disease could improve our understanding of taste pathophysiology, and the prevention of malnutrition by diets adapted to taste impairment.
Published: 2016

39. Food Intake Adaptation to Dietary Fat Involves PSA-Dependent Rewiring of the Arcuate Melanocortin System in Mice

Author: Christophe Guissard, Cecile Hryhorczuk, Caroline Rigault, André Colom, Emmanuelle Nédélec, Luc Pénicaud, Anne Lorsignol, Claude Knauf, Philippe Valet, Alexandra Gouazé, Xavier Fioramonti, Alexandre Benani, Rita Gerardy-Schahn, Alice Krezymon, Thibaut Duparc, Aleth Lemoine, Xavier Brenachot, Jean Gascuel, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Hôpital de Rangueil-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherches sur la Cognition Animale [Toulouse] ( CRCA ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches sur la Cognition Animale (CRCA), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), STROMALab, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), CNRS, Institut National de la Recherche Agronomique, Agence Nationale de la Recherche [ANR-05-PNRA-004], Burgundy county [FABER-2009-9201-AAO036S00635], Association Francaise d'Etudes et de Recherches sur l'Obesite, and Institut B. Delessert
Subjects: Male, MESH: Signal Transduction, Pro-Opiomelanocortin, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, SYNAPTIC INPUT ORGANIZATION, MESH: Energy Intake, Weight Gain, MESH: Mice, Knockout, Mice, 0302 clinical medicine, MESH : Sialic Acids, NPY/AGRP NEURONS, MESH: Pro-Opiomelanocortin, MESH: Animals, MESH : Neuronal Plasticity, MESH: Neuronal Plasticity, PLASTICITY, MESH : Pro-Opiomelanocortin, MESH : Adaptation, Physiological, Mice, Knockout, FEEDING CIRCUITS, MESH : Organ Culture Techniques, INSULIN-RESISTANCE, 0303 health sciences, Neuronal Plasticity, POLYSIALIC ACID, General Neuroscience, Leptin, MESH: Energy Metabolism, digestive, oral, and skin physiology, INDUCED OBESITY, MESH : Sialyltransferases, MESH : Weight Gain, Articles, Adaptation, Physiological, MESH : Mice, Transgenic, BODY-WEIGHT, MESH: Dietary Fats, Hypothalamus, CELL-ADHESION MOLECULE, MESH: Weight Gain, Ghrelin, ENERGY-BALANCE, Melanocortin, hormones, hormone substitutes, and hormone antagonists, Signal Transduction, medicine.medical_specialty, MESH: Mice, Transgenic, MESH : Male, MESH: Sialyltransferases, MESH: Arcuate Nucleus, Mice, Transgenic, MESH : Mice, Inbred C57BL, Biology, MESH : Arcuate Nucleus, MESH: Sialic Acids, 03 medical and health sciences, Organ Culture Techniques, Insulin resistance, MESH: Mice, Inbred C57BL, Arcuate nucleus, Internal medicine, MESH : Mice, medicine, Animals, MESH: Mice, 030304 developmental biology, MESH : Signal Transduction, Arcuate Nucleus of Hypothalamus, MESH : Energy Intake, medicine.disease, Dietary Fats, MESH: Adaptation, Physiological, Sialyltransferases, MESH: Organ Culture Techniques, MESH: Male, Mice, Inbred C57BL, MESH : Energy Metabolism, Endocrinology, MESH: Nerve Net, Sialic Acids, MESH : Nerve Net, MESH : Mice, Knockout, MESH : Animals, Nerve Net, Energy Intake, Energy Metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH : Dietary Fats, 030217 neurology & neurosurgery, Homeostasis, Hormone
Abstract: International audience; Hormones such as leptin and ghrelin can rapidly rewire hypothalamic feeding circuits when injected into rodent brains. These experimental manipulations suggest that the hypothalamus might reorganize continually in adulthood to integrate the metabolic status of the whole body. In this study, we examined whether hypothalamic plasticity occurs in naive animals according to their nutritional conditions. For this purpose, we fed mice with a short-term high-fat diet (HFD) and assessed brain remodeling through its molecular and functional signature. We found that HFD for 3 d rewired the hypothalamic arcuate nucleus, increasing the anorexigenic tone due to activated pro-opiomelanocortin (POMC) neurons. We identified the polysialic acid molecule (PSA) as a mediator of the diet-induced rewiring of arcuate POMC. Moreover, local pharmacological inhibition and genetic disruption of the PSA signaling limits the behavioral and metabolic adaptation to HFD, as treated mice failed to normalize energy intake and showed increased body weight gain after the HFD challenge. Altogether, these findings reveal the existence of physiological hypothalamic rewiring involved in the homeostatic response to dietary fat. Furthermore, defects in the hypothalamic plasticity-driven adaptive response to HFD are obesogenic and could be involved in the development of metabolic diseases.
Published: 2012

40. The Story Learning and Memory (SLAM) test: Equivalence of three forms and sensitivity to left temporal lobe dysfunction

Author: Dominique Piper, Sidonie Pénicaud, Viviane Sziklas, Jelena Djordjevic, Mary Lou Smith, and Marilyn Jones-Gotman
Subjects: Adult, Male, Neuropsychological Tests, Verbal learning, behavioral disciplines and activities, Functional Laterality, Temporal lobe, Young Adult, Behavioral Neuroscience, Epilepsy, medicine, Humans, Equivalence (measure theory), Analysis of Variance, Memory Disorders, Recall, Neuropsychology, Verbal Learning, medicine.disease, Test (assessment), Epilepsy, Temporal Lobe, Neurology, Mental Recall, Female, Neurology (clinical), Verbal memory, Psychology, Cognitive psychology
Abstract: Remembering meaningful information is an important component of verbal memory. However, findings from existing story memory tests have been mixed in patients with temporal lobe epilepsy (TLE). We developed a test, the Story Learning and Memory (SLAM) test, in which a story is presented repeatedly until a performance criterion is reached, and verbatim recall is obtained only once, after a delay. In Study 1 we demonstrated a significant learning deficit in patients with left, but not right, TLE, and they were further impaired in retention of the story despite having learned it to the same criterion as subjects with right TLE and healthy subjects. These deficits remained confined to patients with left TLE after surgery. For clinical use we developed the SLAM in three versions in two languages; in studies 2 and 3 we tested and proved their equivalence.
Published: 2011

41. Tractography of the amygdala and hippocampus: anatomical study and application to selective amygdalohippocampectomy

Author: Taner Tanriverdi, Kelvin Mok, André Olivier, Denise Klein, Sidonie Pénicaud, and Sophie Colnat-Coulbois
Subjects: business.industry, Fornix, Splenium, Hippocampus, General Medicine, Corpus callosum, Amygdala, White matter, medicine.anatomical_structure, medicine, business, Neuroscience, Diffusion MRI, Tractography
Abstract: Object The aim of this study was to evaluate, using diffusion tensor tractography, the white matter fibers crossing the hippocampus and the amygdala, and to perform a volumetric analysis and an anatomical study of the connections of these 2 structures. As a second step, the authors studied the white matter tracts crossing a virtual volume of resection corresponding to a selective amygdalohippocampectomy. Methods Twenty healthy right-handed individuals underwent 3-T MR imaging. Volumetric regions of interest were manually created to delineate the amygdala, the hippocampus, and the volume of resection. White matter fiber tracts were parcellated using the fiber assignment for continuous tracking tractography algorithm. All fibers were registered with the anatomical volumes. Results In all participants, the authors identified fibers following the hippocampus toward the fornix, the splenium of the corpus callosum, and the dorsal hippocampal commissure. With respect to the fibers crossing the amygdala, the authors identified the stria terminalis and the uncinate fasciculus. The virtual resection disrupted part of the fornix, fibers connecting the 2 hippocampi, and fibers joining the orbitofrontal cortex. The approach created a theoretical frontotemporal disconnection and also interrupted fibers joining the temporal pole and the occipital area. Conclusions This diffusion tensor tractography study allowed for good visualization of some of the connections of the amygdala and hippocampus. The authors observed that the virtual selective amygdalohippocampectomy disconnected a large number of fibers connecting frontal, temporal, and occipital areas.
Published: 2010

42. Adipose tissue lymphocytes: types and roles

Author: Sylvie Caspar-Bauguil, L. Castiella, Sandy Bour, Béatrice Cousin, Luc Pénicaud, and Christian Carpéné
Subjects: medicine.medical_specialty, Time Factors, Physiology, Lymphocyte, Adipose tissue, White adipose tissue, Biology, Models, Biological, Biochemistry, Fat pad, Proinflammatory cytokine, Mice, Immune system, Adipokines, Internal medicine, Diabetes Mellitus, medicine, Animals, Humans, Lymphocytes, Obesity, Inflammation, Innate immune system, General Medicine, Acquired immune system, medicine.anatomical_structure, Endocrinology, Adipose Tissue, Immune System, Immunology
Abstract: Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.
Published: 2009

43. Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signaling

Author: Géraldine Offer, Alexandre Benani, Lionel Carneiro, Tristan Jaillard, Christophe Magnan, Louis Casteilla, Anne Lorsignol, Corinne Leloup, Anne-Laure Colombani, Anne Galinier, Luc Pénicaud, and Thibaut Duparc
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Hypothalamus, Respiratory chain, Action Potentials, Oxidative phosphorylation, Mitochondrion, Oxidative Phosphorylation, Superoxide dismutase, chemistry.chemical_compound, Oxygen Consumption, Internal medicine, Hypersensitivity, Internal Medicine, medicine, Animals, Homeostasis, Obesity, Aconitate Hydratase, chemistry.chemical_classification, Reactive oxygen species, biology, Insulin, Glutathione peroxidase, Brain, Glutathione, Mitochondria, Rats, Rats, Zucker, Metabolism, Glucose, Endocrinology, chemistry, biology.protein, Original Article, Oxidation-Reduction, Signal Transduction
Abstract: OBJECTIVE Recent data demonstrated that glucose sensing in different tissues is initiated by an intracellular redox signaling pathway in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the present study was to determine whether brain glucose hypersensitivity present in obese Zücker rats is related to an alteration in redox signaling. RESEARCH DESIGN AND METHODS Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus, changes in reactive oxygen species levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modifications of redox state and mitochondrial functions were assessed through oxidized glutathione, glutathione peroxidase, manganese superoxide dismutase, aconitase activities, and mitochondrial respiration. RESULTS Hypothalamic hypersensitivity to glucose was characterized by enhanced electrical activity of the arcuate nucleus and increased insulin secretion at a low glucose concentration, which does not produce such an effect in normal rats. It was associated with 1) increased reactive oxygen species levels in response to this low glucose load, 2) constitutive oxidized environment coupled with lower antioxidant enzyme activity at both the cellular and mitochondrial level, and 3) overexpression of several mitochondrial subunits of the respiratory chain coupled with a global dysfunction in mitochondrial activity. Moreover, pharmacological restoration of the glutathione hypothalamic redox state by reduced glutathione infusion in the third ventricle fully reversed the cerebral hypersensitivity to glucose. CONCLUSIONS The data demonstrated that obese Zücker rats' impaired hypothalamic regulation in terms of glucose sensing is linked to an abnormal redox signaling, which originates from mitochondria dysfunction.
Published: 2009

44. Preconditioning by Mitochondrial Reactive Oxygen Species Improves the Proangiogenic Potential of Adipose-Derived Cells-Based Therapy

Author: Luc Pénicaud, Mireille André, Samuel Arnal, Yvette Fernandez, Bernard I. Levy, Jean-Sébastien Silvestre, Valérie Planat-Benard, Micheline Duriez, Emmanuelle Arnaud, Stephanie Dehez, Louis Casteilla, Audrey Carrière, Téni G. Ebrahimian, Carine Joffre, Nathalie Augé, Corinne Barreau, Développement et Communication Chimique chez les Insectes (DCCI), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Développement et Communication Chimique chez les Insectes ( DCCI ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and Delon, Viviane
Subjects: Male, Mitochondrial ROS, Programmed cell death, Stromal Cells/cytology/metabolism, Angiogenesis, Cells, Reactive Oxygen Species/*metabolism, Neovascularization, Physiologic, Biology, Mitochondrion, medicine.disease_cause, Mice, 03 medical and health sciences, 0302 clinical medicine, Adipocytes, medicine, Animals, Endothelial Cells/*cytology/*physiology, Cells, Cultured, Neovascularization, 030304 developmental biology, Mitochondria/*metabolism, chemistry.chemical_classification, Reperfusion Injury/physiopathology, 0303 health sciences, Reactive oxygen species, Cultured, Endothelial Cells, Cell Differentiation, Mitochondria, Cell biology, Cell Differentiation/*physiology, Transplantation, Physiologic/*physiology, chemistry, Reperfusion Injury, 030220 oncology & carcinogenesis, Immunology, Stromal Cells, Stem cell, Reactive Oxygen Species, Cardiology and Cardiovascular Medicine, Oxidative stress
Abstract: Objective— Transplantation of adipose-derived stroma cells (ADSCs) stimulates neovascularization after experimental ischemic injury. ADSC proangiogenic potential is likely mediated by their ability to differentiate into endothelial cells and produce a wide array of angiogenic and antiapoptotic factors. Mitochondrial reactive oxygen species (ROS) have been shown to control ADSC differentiation. We therefore hypothesized that mitochondrial ROS production may change the ADSC proangiogenic properties. Methods and Results— The use of pharmacological strategies (mitochondrial inhibitors, antimycin, and rotenone, with or without antioxidants) allowed us to specifically and precisely modulate mitochondrial ROS generation in ADSCs. We showed that transient stimulation of mitochondrial ROS generation in ADSCs before their injection in ischemic hindlimb strongly improved revascularization and the number of ADSC-derived CD31-positive cells in ischemic area. Mitochondrial ROS generation increased the secretion of the proangiogenic and antiapoptotic factors, VEGF and HGF, but did not affect ADSC ability to differentiate into endothelial cells, in vitro. Moreover, mitochondrial ROS-induced ADSC preconditioning greatly protect ADSCs against oxidative stress-induced cell death. Conclusion— Our study demonstrates that in vitro preconditioning by moderate mitochondrial ROS generation strongly increases in vivo ADSC proangiogenic properties and emphasizes the crucial role of mitochondrial ROS in ADSC fate.
Published: 2009

45. Hypothalamic Reactive Oxygen Species Are Required for Insulin-Induced Food Intake Inhibition

Author: Alexandre Benani, Anne Lorsignol, Louis Casteilla, Corinne Leloup, Michael Roger, Tristan Jaillard, Pascale Guillou, Anne Galinier, and Luc Pénicaud
Subjects: chemistry.chemical_classification, Reactive oxygen species, medicine.medical_specialty, Antioxidant, NADPH oxidase, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, media_common.quotation_subject, Insulin, Appetite, Biology, Energy homeostasis, Endocrinology, chemistry, Internal medicine, Internal Medicine, medicine, biology.protein, Homeostasis, Pancreatic hormone, media_common
Abstract: OBJECTIVE Insulin plays an important role in the hypothalamic control of energy balance, especially by reducing food intake. Emerging data point to a pivotal role of reactive oxygen species (ROS) in energy homeostasis regulation, but their involvement in the anorexigenic effect of insulin is unknown. Furthermore, ROS signal derived from NADPH oxidase activation is required for physiological insulin effects in peripheral cells. In this study, we investigated the involvement of hypothalamic ROS and NADPH oxidase in the feeding behavior regulation by insulin. RESEARCH DESIGN AND METHODS We first measured hypothalamic ROS levels and food intake after acute intracerebroventricular injection of insulin. Second, effect of pretreatment with a ROS scavenger or an NADPH oxidase inhibitor was evaluated. Third, we examined the consequences of two nutritional conditions of central insulin unresponsiveness (fasting or short-term high-fat diet) on the ability of insulin to modify ROS level and food intake. RESULTS In normal chow-fed mice, insulin inhibited food intake. At the same dose, insulin rapidly and transiently increased hypothalamic ROS levels by 36%. The pharmacological suppression of this insulin-stimulated ROS elevation, either by antioxidant or by an NADPH oxidase inhibitor, abolished the anorexigenic effect of insulin. Finally, in fasted and short-term high-fat diet–fed mice, insulin did not promote elevation of ROS level and food intake inhibition, likely because of an increase in hypothalamic diet-induced antioxidant defense systems. CONCLUSIONS A hypothalamic ROS increase through NADPH oxidase is required for the anorexigenic effect of insulin.
Published: 2009

46. S 26948

Author: Nathalie Hennuyer, Maria Carmen Carmona, Louis Casteilla, Luc Pénicaud, Bart Staels, Pierre Renard, Gérard Torpier, Bruno Lefebvre, Catherine Fievet, Katie Louche, Pierre Formstecher, Véronique Audinot-Bouchez, Catherine Dacquet, Antoine Pilon, and Philippe Lefebvre
Subjects: chemistry.chemical_classification, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Peroxisome proliferator-activated receptor, Biology, Pharmacology, chemistry.chemical_compound, Endocrinology, chemistry, Lipid oxidation, Adipogenesis, In vivo, Internal medicine, Adipocyte, Coactivator, Internal Medicine, medicine, Receptor, Rosiglitazone, medicine.drug
Abstract: OBJECTIVE—Rosiglitazone displays powerful antidiabetes benefits but is associated with increased body weight and adipogenesis. Keeping in mind the concept of selective peroxisome proliferator–activated receptor (PPAR)γ modulator, the aim of this study was to characterize the properties of a new PPARγ ligand, S 26948, with special attention in body-weight gain. RESEARCH DESIGN AND METHODS—We used transient transfection and binding assays to characterized the binding characteristics of S 26948 and GST pull-down experiments to investigate its pattern of coactivator recruitment compared with rosiglitazone. We also assessed its adipogenic capacity in vitro using the 3T3-F442A cell line and its in vivo effects in ob/ob mice (for antidiabetes and antiobesity properties), as well as the homozygous human apolipoprotein E2 knockin mice (E2-KI) (for antiatherogenic capacity). RESULTS—S 26948 displayed pharmacological features of a high selective ligand for PPARγ with low potency in promoting adipocyte differentiation. It also displayed a different coactivator recruitment profile compared with rosiglitazone, being unable to recruit DRIP205 or PPARγ coactivator-1α. In vivo experiments showed that S 26948 was as efficient in ameliorating glucose and lipid homeostasis as rosiglitazone, but it did not increase body and white adipose tissue weights and improved lipid oxidation in liver. In addition, S 26948 represented one of the few molecules of the PPARγ ligand class able to decrease atherosclerotic lesions. CONCLUSIONS—These findings establish S 26948 as a selective PPARγ ligand with distinctive coactivator recruitment and gene expression profile, reduced adipogenic effect, and improved biological responses in vivo.
Published: 2007

47. Characterization of Glucosensing Neuron Subpopulations in the Arcuate Nucleus

Author: Luc Pénicaud, Anne Lorsignol, Sylvain Contie, Xavier Fioramonti, Vanessa H. Routh, and Zhentao Song
Subjects: medicine.medical_specialty, Arc (protein), Endocrinology, Diabetes and Metabolism, Biology, Neuropeptide Y receptor, chemistry.chemical_compound, medicine.anatomical_structure, Endocrinology, nervous system, chemistry, Hypothalamus, Arcuate nucleus, Internal medicine, Internal Medicine, medicine, Extracellular, Neuron, Melanocortin, Neurotransmitter
Abstract: Four types of responses to glucose changes have been described in the arcuate nucleus (ARC): excitation or inhibition by low glucose concentrations 5 mmol/l (high glucose–excited and –inhibited neurons). However, the ability of the same ARC neuron to detect low and high glucose concentrations has never been investigated. Moreover, the mechanism involved in mediating glucose sensitivity in glucose-inhibited neurons and the neurotransmitter identity (neuropeptide Y [NPY] or pro-opio melanocortin [POMC]) of glucosensing neurons has remained controversial. Using patch-clamp recordings on acute mouse brain slices, successive extracellular glucose changes greater than and less than 5 mmol/l show that glucose-excited, high glucose–excited, glucose-inhibited, and high glucose–inhibited neurons are different glucosensing cell subpopulations. Glucose-inhibited neurons directly detect decreased glucose via closure of a chloride channel. Using transgenic NPY–green fluorescent protein (GFP) and POMC-GFP mice, we show that 40% of NPY neurons are glucose-inhibited neurons. In contrast, 5 mmol/l. In vivo results confirm the lack of glucose sensitivity of POMC neurons. Taken together, hypo- and hyperglycemia are detected by distinct populations of glucosensing neurons, and POMC and NPY neurons are not solely responsible for ARC glucosensing.
Published: 2007

48. Overexpression of Adiponectin Targeted to Adipose Tissue in Transgenic Mice: Impaired Adipocyte Differentiation

Author: Marie-Christine Many, Maximin Senou, Isabelle B. Bauche, Luc Pénicaud, Anne-Marie Pottier, Sonia Brichard, René Rezsohazy, Norikazu Maeda, Tohru Funahashi, and Samira Ait El Mkadem
Subjects: Male, medicine.medical_specialty, Cellular differentiation, Transgene, Adipose tissue, Adipokine, Mice, Transgenic, White adipose tissue, Biology, Fatty Acid-Binding Proteins, Cell Line, Mice, chemistry.chemical_compound, Endocrinology, Enhancer binding, Adipocyte, Internal medicine, Adipocytes, medicine, Animals, Adiponectin, Cell Differentiation, Mice, Inbred C57BL, Glucose, Adipose Tissue, chemistry, Organ Specificity, Female, Energy Metabolism
Abstract: Adiponectin (ApN) is an adipokine whose expression and plasma levels are inversely related to obesity and insulin-resistant states. Chronic repercussions of ApN treatment or overexpression on adiposity and body weight are still controversial. Here, we generated a transgenic (Tg) mouse model allowing persistent and moderate overexpression of native full-length ApN targeted to white adipose tissue. Adipose mass and adipocyte size of Tg mice were reduced despite preserved calorie intake. This reduction resulted from increased energy expenditure and up-regulation of uncoupling proteins, and from abrogation of the adipocyte differentiation program, as shown by the loss of a key lipogenic enzyme and of adipocyte markers. Adipose mass remodeling favors enhanced insulin sensitivity and improved lipid profile of Tg mice. Alteration of the adipocyte phenotype was likely to result from increased expression of the preadipocyte factor-1 and from down-regulation of the transcription factor, CCAAT/enhancer binding protein-alpha, which orchestrates adipocyte differentiation. We further found that recombinant ApN directly stimulated pre- adipocyte factor-1 mRNA and attenuated CCAAT/enhancer binding protein-alpha expression in cultured 3T3-F442A cells. Conversely, opposite changes in the expression of these genes were observed in white fat of ApN-deficient mice. Thus, besides enhanced energy expenditure, our work shows that impairment of adipocyte differentiation contributes to the anti-adiposity effect of ApN.
Published: 2007

49. Role for Mitochondrial Reactive Oxygen Species in Brain Lipid Sensing

Author: Maria Carmen Carmona, Xavier Fioramonti, Corinne Leloup, Louis Casteilla, Luc Pénicaud, Alexandre Benani, Stéphanie Troy, and Anne Lorsignol
Subjects: chemistry.chemical_classification, Mitochondrial ROS, medicine.medical_specialty, Reactive oxygen species, Cell signaling, Endocrinology, Diabetes and Metabolism, digestive, oral, and skin physiology, Hypertriglyceridemia, nutritional and metabolic diseases, Nutrient sensing, Metabolism, Mitochondrion, Biology, medicine.disease, Endocrinology, chemistry, Internal medicine, Internal Medicine, medicine, Intracellular
Abstract: The ability for the brain to sense peripheral fuel availability is mainly accomplished within the hypothalamus, which detects ongoing systemic nutrients and adjusts food intake and peripheral metabolism as needed. Here, we hypothesized that mitochondrial reactive oxygen species (ROS) could trigger sensing of nutrients within the hypothalamus. For this purpose, we induced acute hypertriglyceridemia in rats and examined the function of mitochondria in the hypothalamus. Hypertriglyceridemia led to a rapid increase in the mitochondrial respiration in the ventral hypothalamus together with a transient production of ROS. Cerebral inhibition of fatty acids–CoA mitochondrial uptake prevented the hypertriglyceridemia-stimulated ROS production, indicating that ROS derived from mitochondrial metabolism. The hypertriglyceridemia-stimulated ROS production was associated with change in the intracellular redox state without any noxious cytotoxic effects, suggesting that ROS function acutely as signaling molecules. Moreover, cerebral inhibition of hypertriglyceridemia-stimulated ROS production fully abolished the satiety related to the hypertriglyceridemia, suggesting that hypothalamic ROS production was required to restrain food intake during hypertriglyceridemia. Finally, we found that fasting disrupted the hypertriglyceridemia-stimulated ROS production, indicating that the redox mechanism of brain nutrient sensing could be modulated under physiological conditions. Altogether, these findings support the role of mitochondrial ROS as molecular actors implied in brain nutrient sensing.
Published: 2007

50. Vascular fate of adipose tissue-derived adult stromal cells in the ischemic murine brain: A combined imaging-histological study

Author: Louis Casteilla, Bartosz Karaszewski, Mireille André, Elisabeth Pinard, Jean-Sébastien Silvestre, Yutaka Tomita, Valérie Planat-Benard, Ludovic Waeckel, Jacques Seylaz, Alexy Tran-Dinh, Nathalie Kubis, and Luc Pénicaud
Subjects: Pathology, medicine.medical_specialty, Stromal cell, Cognitive Neuroscience, Adipose tissue, Biology, Brain Ischemia, Green fluorescent protein, Mice, Inbred C57BL, Lesion, Mice, medicine.anatomical_structure, Adipose Tissue, Neurology, Cell Movement, In vivo, Cortex (anatomy), medicine, Animals, Basal lamina, Stromal Cells, Progenitor cell, medicine.symptom
Abstract: Increasing evidence indicates that fat tissue can provide a novel source of progenitor cells with therapeutic potential. Here, the fate of adipose tissue-derived stromal cells (ADSCs) transplanted into the mouse ischemic cortex was monitored in the long term using in vivo imaging, and subsequently characterized. The left middle cerebral artery (MCA) was occluded in C57BL/6J mice equipped with a closed cranial window chronically implanted over the left parietal cortex (n = 20). ADSCs expressing the green fluorescent protein (GFP) (approximately 18 × 103 cells in 0.5 μl) were transplanted into the ipsilateral cortex, 24 h after MCA occlusion. GFP+-ADSCs were monitored through the window using confocal fluorescence microscopy to assess their single fate in vivo. Co-localization of GFP with vascular, neuronal, glial or proliferation markers was investigated immunohistochemically. Repeated in vivo imaging revealed that GFP+-ADSCs migrated over 1 week toward the lesion, survived for at least 4 weeks, and exhibited a particular tropism for vessels. About 5% of the transplanted GFP+-ADSCs were scattered in the peri-ischemic area on histological sections. Immunohistochemistry evidenced that perivascular GFP+-ADSCs enfolded CD31-labeled endothelial cells, always outside their basal lamina, and occasionally expressed smooth muscle alpha-actin. Less than 1% GFP and BrdU co-labeling indicated a low proliferation rate of ADSCs. These results demonstrate that cerebral ischemia induces ADSCs survival, migration toward the lesion, especially toward microvessels, and occasional differentiation into smooth muscle cells.
Published: 2007

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