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18 results on '"Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME)"'

1. Coenzyme Q as an antiadipogenic factor

Author

Luc Van Gaal, Anne Galinier, Louis Casteilla, Luc Pénicaud, Bart Staels, Sandy Bour, Maria-Carmen Carmona, Sylvie Caspar-Bauguil, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Antwerp University Hospital [Edegem] (UZA), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-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), Antwerp University Hospital, Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-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), 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 ), Neurobiologie, plasticité tissulaire et métabolisme énergétique ( NPTME ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Antwerp University Hospital [Edegem], Récepteurs nucléaires, maladies cardiovasculaires et diabète ( EGID ), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), and 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 )

Subjects
Male, Antioxidant, muscle, medicine.medical_treatment, Cellular differentiation, coq(10) deficiency, MESH : Adipocytes, White adipose tissue, Biochemistry, Antioxidants, Mice, 0302 clinical medicine, q(10) deficiency, Adipocyte, MESH: Animals, Enzyme Inhibitors, MESH: Mice, Obese, MESH : Body Weight, General Environmental Science, 0303 health sciences, Adipogenesis, MESH : Adipogenesis, food and beverages, MESH : Mice, Obese, MESH : Ubiquinone, MESH : alpha-Tocopherol, MESH : Antioxidants, MESH : Cell Differentiation, MESH: Adipose Tissue, medicine.medical_specialty, MESH: Alkyl and Aryl Transferases, MESH : Adipose Tissue, MESH : Quinones, 03 medical and health sciences, Humans, Molecular Biology, MESH: Adipocytes, Alkyl and Aryl Transferases, MESH: Humans, [ SDV ] Life Sciences [q-bio], MESH : Humans, MESH: Antioxidants, MESH : Organ Size, MESH: Body Weight, MESH: Cell Line, Mice, Inbred C57BL, Endocrinology, chemistry, Human medicine, Reactive Oxygen Species, MESH: Female, MESH : Dietary Fats, 030217 neurology & neurosurgery, MESH : Cell Line, obesity, Physiology, Ubiquinone, MESH: Organ Size, [SDV]Life Sciences [q-bio], Clinical Biochemistry, alpha-Tocopherol, MESH : Reactive Oxygen Species, Adipose tissue, Mice, Obese, rosiglitazone, chemistry.chemical_compound, Adipocytes, oxidative stress, MESH: Obesity, MESH : Female, MESH: Ubiquinone, Quinones, MESH: Reactive Oxygen Species, Cell Differentiation, Organ Size, adipose tissue, MESH: alpha-Tocopherol, MESH: Enzyme Inhibitors, MESH: Dietary Fats, MESH : Obesity, Female, MESH: Cell Differentiation, uncoupling protein 2, MESH : Male, MESH : Mice, Inbred C57BL, mitochondrial encephalomyopathy, Biology, MESH: Quinones, Cell Line, MESH: Mice, Inbred C57BL, Internal medicine, MESH : Mice, expression, medicine, Animals, MESH: Mice, MESH : Alkyl and Aryl Transferases, 030304 developmental biology, MESH : Enzyme Inhibitors, Body Weight, Cell Biology, Dietary Fats, MESH: Male, Cell culture, Coenzyme Q – cytochrome c reductase, General Earth and Planetary Sciences, MESH : Animals, MESH: Adipogenesis
Abstract

WOS: 000285876900007; International audience; Coenzyme Q (CoQ) is not only the single antioxidant synthesized in humans but also an obligatory element of mitochondrial functions. We have previously reported CoQ deficiency in white adipose tissue of ob/ob mice. We sought to determine (i) whether this deficit exists in all species and its relevance in human obesity and (ii) to what extent CoQ could be involved in adipocyte differentiation. Here we identified in rodents as well as in humans a specific very strong nonlinear negative correlation between CoQ content in subcutaneous adipose tissue and obesity indexes. This striking correlation reveals a threshold value similar in both species. This relative deficit in CoQ content in adipose tissue rapidly took place during the time course of high-fat-diet-induced obesity in mice. Adipocyte differentiation was assessed in vitro using the preadipocyte 3T3-F442A cell line. When CoQ synthesis was inhibited by a pharmacological approach using chlorobenzoic acid, this strongly triggered adipose differentiation. In contrast, adipogenesis was strongly inhibited when a long-term increase in CoQ content was obtained by overexpressing human 4-hydroxy benzoate acid polyprenyltransferase gene. Altogether, these data suggest that a strict level of CoQ remains essential for adipocyte differentiation, and its impairment is associated with obesity.

Published
2011

2. Balancing mitochondrial redox signaling: a key point in metabolic regulation

Author

Audrey Carrière, Corinne Leloup, Lionel Carneiro, Luc Pénicaud, Louis Casteilla, Anne Galinier, Alexandre Benani, 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 ), Neurobiologie, plasticité tissulaire et métabolisme énergétique ( NPTME ), 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), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)

Subjects
Blood Glucose, MESH: Oxidation-Reduction, MESH: Signal Transduction, Physiology, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Cell, MESH: Neurons, Adipose tissue, MESH : Reactive Oxygen Species, Biochemistry, Ion Channels, MESH: Insulin-Secreting Cells, 0302 clinical medicine, Insulin-Secreting Cells, Uncoupling Protein 2, MESH: Animals, General Environmental Science, Neurons, chemistry.chemical_classification, 0303 health sciences, Adipogenesis, MESH : Adipogenesis, MESH: Reactive Oxygen Species, MESH: Mitochondrial Proteins, Mitochondria, Cell biology, medicine.anatomical_structure, MESH : Mitochondria, Oxidation-Reduction, MESH : Ion Channels, Signal Transduction, Cell type, medicine.medical_specialty, Cell signaling, MESH : Hypothalamus, MESH: Mitochondria, Hypothalamus, Context (language use), Biology, MESH : Neurons, Mitochondrial Proteins, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, Molecular Biology, MESH : Mitochondrial Proteins, 030304 developmental biology, MESH : Oxidation-Reduction, MESH : Signal Transduction, Reactive oxygen species, MESH: Humans, [ SDV ] Life Sciences [q-bio], Mechanism (biology), MESH : Humans, MESH : Insulin-Secreting Cells, Cell Biology, MESH : Blood Glucose, MESH: Hypothalamus, Endocrinology, Metabolic regulation, chemistry, MESH: Ion Channels, MESH: Blood Glucose, General Earth and Planetary Sciences, MESH : Animals, Reactive Oxygen Species, MESH: Adipogenesis, 030217 neurology & neurosurgery
Abstract

WOS: 000285876900015; International audience; Mitochondrial reactive oxygen species (mROS) have emerged as signaling molecules in physiology primarily as a result of studies of uncoupling mechanisms in mitochondrial respiration. The discovery that this mechanism negatively regulates mROS generation in many cell types has drawn the attention of the scientific community to the pathological consequences of excess mROS production. From reports of the energetic fluxes in cells grown under normal conditions, the hypothesis that mROS are an integrated physiological signal of the metabolic status of the cell has emerged. Here, we consider recent studies that support this point of view in two key nutrient sensors of the body, beta cells and the hypothalamus, which are the main coordinators of endocrine and nervous controls of energy metabolism and adipose tissue, which is of paramount importance in controlling body weight and, therefore, the development of obesity and type 2 diabetes. In this context, finely balanced mROS production may be at the core of proper metabolic maintenance, and unbalanced mROS production, which is largely documented, might be an important trigger of metabolic disorders.

Published
2011

3. Mitochondrial reactive oxygen species are obligatory signals for glucose-induced insulin secretion

Author

Melis Karaca, Julien Castel, Luc Pénicaud, Christophe Magnan, Lionel Carneiro, Corinne Leloup, Anne-Laure Colombani, Louis Casteilla, Alain Ktorza, Cécile Tourrel-Cuzin, Delon, Viviane, 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, Laboratoire de physiopathologie de la nutrition ( LPN ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche sur les Ions, les MAtériaux et la Photonique ( CIMAP - UMR 6252 ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Ecole Nationale Supérieure d'Ingénieurs de Caen ( ENSICAEN ), Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie, plasticité tissulaire et métabolisme énergétique ( NPTME ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Développement et Communication Chimique chez les Insectes (DCCI), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur les Ions, les MAtériaux et la Photonique (CIMAP - UMR 6252), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), 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, Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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 National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)

Subjects
Male, Mitochondrial ROS, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, chemistry.chemical_element, Calcium, Mitochondrion, Biology, Superoxide dismutase, Islets of Langerhans, 03 medical and health sciences, chemistry.chemical_compound, Adenosine Triphosphate, 0302 clinical medicine, Superoxides, Internal medicine, Insulin Secretion, Internal Medicine, medicine, Animals, Insulin, Secretion, Chromans, Rats, Wistar, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Superoxide Dismutase, Superoxide, NAD, Mitochondria, Rats, Kinetics, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Glucose, Endocrinology, Islet Studies, chemistry, biology.protein, Thapsigargin, Reactive Oxygen Species, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Signal Transduction
Abstract

OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion. RESEARCH DESIGN AND METHODS—ROS production in response to glucose was investigated in freshly isolated rat islets. ROS effects were studied using a pharmacological approach and calcium imaging. RESULTS—Transient glucose increase from 5.5 to 16.7 mmol/l stimulated ROS generation, which was reversed by antioxidants. Insulin secretion was dose dependently blunted by antioxidants and highly correlated with ROS levels. The incapacity of β-cells to secrete insulin in response to glucose with antioxidants was associated with a decrease in ROS production and in contrast to the maintenance of high levels of ATP and NADH. Then, we investigated the mitochondrial origin of ROS (mROS) as the triggering signal. Insulin release was mimicked by the mitochondrial-complex blockers, antimycin and rotenone, that generate mROS. The adding of antioxidants to mitochondrial blockers or to glucose was used to lower mROS reversed insulin secretion. Finally, calcium imaging on perifused islets using glucose stimulation or mitochondrial blockers revealed that calcium mobilization was completely reversed using the antioxidant trolox and that it was of extracellular origin. No toxic effects were present using these pharmacological approaches. CONCLUSIONS—Altogether, these complementary results demonstrate that mROS production is a necessary stimulus for glucose-induced insulin secretion.

Published
2009

4. Immunocytochemical localization of the glucose transporter 2 (GLUT2) in the adult rat brain. II. Electron microscopic study

Author

Corinne Leloup, Bernard Thorens, Luc Pénicaud, Monique Quignon, Michel Arluison, Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre des Sciences du Goût (CSG), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31] (LMPM), IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU 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), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), 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), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), 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 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 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), Neurobiologie des signaux intercellulaires ( NSI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -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 ), Métabolisme, plasticité et mitochondrie, Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR31-Centre National de la Recherche Scientifique ( CNRS ), Neurobiologie, plasticité tissulaire et métabolisme énergétique ( NPTME ), and Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Male, endocrine system, Dendritic spine, Monosaccharide Transport Proteins, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Dendritic Spines, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, ultrastructural level, oligodendrocytes, Biology, nerve terminals, blood vessels, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Microscopy, Electron, Transmission, glucose-sensitive neurones, medicine, Animals, Neurotransmitter, dendritic shafts, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Glucose Transporter Type 2, 0303 health sciences, astrocytes, Brain, Immunohistochemistry, Oligodendrocyte, Rats, Oligodendroglia, medicine.anatomical_structure, chemistry, Forebrain, biology.protein, GLUT2, Nucleus, Neuroscience, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, Immunostaining, Astrocyte
Abstract

International audience; Following a former immunohistochemical study in the rat brain [Arluison, M., Quignon, M., Nguyen, P., Thorens, B., Leloup, C., Pénicaud, L. Distribution and anatomical localization of the glucose transporter 2 (GLUT2) in the adult rat brain. I. Immunohistochemical study. J. Chem. Neuroanat., in press], we have analyzed the ultrastructural localization of GLUT2 in representative and/or critical areas of the forebrain and hindbrain. In agreement with previous results, we observe few oligodendrocyte and astrocyte cell bodies discretely labeled for GLUT2 in large myelinated fibre bundles and most brain areas examined, whereas the reactive glial processes are more numerous and often localized in the vicinity of nerve terminals and/or dendrites or dendritic spines forming synaptic contacts. Only some of them appear closely bound to unlabeled nerve cell bodies and dendrites. Furthermore, the nerve cell bodies prominently immunostained for GLUT2 are scarce in the brain nuclei examined, whereas the labeled dendrites and dendritic spines are relatively numerous and frequently engaged in synaptic junctions. In conformity with the observation of GLUT2-immunoreactive rings at the periphery of numerous nerve cell bodies in various brain areas (see previous paper), we report here that some neuronal perikarya of the dorsal endopiriform nucleus/perirhinal cortex exhibit some patches of immunostaining just below the plasma membrane. However, the presence of many GLUT2-immunoreactive nerve terminals and/or astrocyte processes, some of them being occasionally attached to nerve cell bodies and dendrites, could also explain the pericellular labeling observed. The results here reported support the idea that GLUT2 may be expressed by some cerebral neurones possibly involved in glucose sensing, as previously discussed. However, it is also possible that this transporter participate in the regulation of neurotransmitter release and, perhaps, in the release of glucose by glial cells.

Published
2004

5. Human adipose stromal-vascular fraction self-organizes to form vascularized adipose tissue in 3D cultures

Author

Frédéric Deschaseaux, Pauline Achard, Audrey Carrière, Justine Creff, Hélène Leménager, Isabelle Ader, Luc Sensebé, Sandra Muller, 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), Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), 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 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), Université Fédérale Toulouse Midi-Pyrénées, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Etablissement français du sang [Pyrénées-Méditerranée] (EFS Pyrénées-Méditerranée), Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UPS), 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), Équipe Ingénierie pour les sciences du vivant (LAAS-ELIA), Laboratoire d'analyse et d'architecture des systèmes [Toulouse] (LAAS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UPS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UPS), Etablissement Français du Sang Pyrénées Méditerranée (EFS), CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], 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, Cell biology, Stromal cell, Adipose Tissue, White, [SDV]Life Sciences [q-bio], lcsh:Medicine, Mice, Nude, Adipose tissue, Stem cells, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, In vivo, Spheroids, Cellular, Adipocytes, Organoid, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Obesity, Progenitor cell, lcsh:Science, Adiposity, Adipogenesis, Multidisciplinary, Tissue Engineering, Chemistry, lcsh:R, Spheroid, Endothelial Cells, Cell Differentiation, Stromal vascular fraction, Coculture Techniques, Organoids, 030104 developmental biology, lcsh:Q, Female, Stromal Cells, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Native human subcutaneous adipose tissue (AT) is well organized into unilocular adipocytes interspersed within dense vascularization. This structure is completely lost under standard culture conditions and may impair the comparison with native tissue. Here, we developed a 3-D model of human white AT reminiscent of the cellular architecture found in vivo. Starting with adipose progenitors derived from the stromal-vascular fraction of human subcutaneous white AT, we generated spheroids in which endogenous endothelial cells self-assembled to form highly organized endothelial networks among stromal cells. Using an optimized adipogenic differentiation medium to preserve endothelial cells, we obtained densely vascularized spheroids containing mature adipocytes with unilocular lipid vacuoles. In vivo study showed that when differentiated spheroids were transplanted in immune-deficient mice, endothelial cells within the spheroids connected to the recipient circulatory system, forming chimeric vessels. In addition, adipocytes of human origin were still observed in transplanted mice. We therefore have developed an in vitro model of vascularized human AT-like organoids that constitute an excellent tool and model for any study of human AT.

Published
2019

6. The Release of Adipose Stromal Cells from Subcutaneous Adipose Tissue Regulates Ectopic Intramuscular Adipocyte Deposition

Author

Quentin Sastourné-Arrey, Célia Bergeaud, Louis Casteilla, Emmanuelle Arnaud, Jean Philippe Pradère, Cedric Moro, Virginie Bourlier, Noémie Juin, Marta Gil-Ortega, Coralie Sengenès, Corinne Barreau, Julie Vion, Amandine Girousse, Christophe Guissard, 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), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), University of British Columbia (UBC), Service de Pharmacologie Clinique, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Unité de recherche sur les obésités, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-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 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)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR 31 Louis Bugnard (IFR 31), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, medicine.medical_specialty, Stromal cell, Subcutaneous Fat, Adipose tissue, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Adipocyte, Lipid droplet, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Progenitor cell, lcsh:QH301-705.5, Progenitor, Skeletal muscle, medicine.disease, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, lcsh:Biology (General), Intramuscular Absorption, chemistry, Stromal Cells, 030217 neurology & neurosurgery
Abstract

Summary: Ectopic lipid deposition (ELD) is defined by excess fat storage in locations not classically associated with adipose tissue (AT) storage. ELD is positively correlated with insulin resistance and increased risk of metabolic disorders. ELD appears as lipid droplets or adipocytes, whose cell origin is unknown. We previously showed that subcutaneous AT (ScAT) releases adipocyte progenitors into the circulation. Here, we demonstrate that triggering or preventing the release of adipocyte precursors from ScAT directly promoted or limited ectopic adipocyte formation in skeletal muscle in mice. Importantly, obesity-associated metabolic disorders could be mimicked by causing adipocyte precursor release without a high-fat diet. Finally, during nutrient overload, adipocyte progenitors exited ScAT, where their retention signals (CXCR4/CXCL12 axis) were greatly decreased, and further infiltrated skeletal muscles. These data provide insights into the formation of ELD associated with calorie overload and highlight adipocyte progenitor trafficking as a potential target in the treatment of metabolic diseases. : Girousse et al. show that, in mice fed a high-fat diet, adipose stromal cells (ASCs) can egress subcutaneous adipose tissue and infiltrate skeletal muscle to form ectopic adipocytes, causing metabolic disturbance. ASC trafficking is regulated by the CXCR4/CXCL12 axis, and pioglitazone intermittent treatment can prevent muscle ectopic lipid deposition. Keywords: ectopic adipocytes, adipose stem or stromal cells, intramuscular adipocyte, thiazolidinedione, type 2 diabetes, CXCR4/CXCL12, AMD3100, lymphatic system, chemotaxis

Published
2019

7. Differentiation of Human Induced Pluripotent Stem Cells into Brown and White Adipocytes: Role of Pax3

Author

B. Chignon-Sicard, Audrey Carrière, Austin Smith, Christian Dani, Louis Casteilla, Tala Mohsen-Kanson, Maria Svensson, Claude Bagnis, Brigitte Wdziekonski, Phi Villageois, Anne-Laure Hafner, Per-Arne Svensson, Yasuhiro Takashima, Institut de Biologie Valrose (IBV), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre for Stem Cell Research, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, 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 Development in Stem Cell Biology, University of Edinburgh-Institute for Stem Cell Research, Institute for Stem Cell Biology, University of Cambridge [UK] (CAM), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), 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), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), 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
Male, [SDV]Life Sciences [q-bio], Adipocytes, White, Induced Pluripotent Stem Cells, Tretinoin, White adipose tissue, Biology, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Adipocyte, Animals, Humans, Paired Box Transcription Factors, Progenitor cell, Induced pluripotent stem cell, PAX3 Transcription Factor, Transcription factor, 030304 developmental biology, Aged, 80 and over, Genetics, PRDM16, 0303 health sciences, Adipogenesis, Cell Differentiation, Cell Biology, Phenotype, Cell biology, Adipocytes, Brown, chemistry, embryonic structures, Molecular Medicine, Female, Ectopic expression, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Identification of molecular mechanisms involved in generation of different types of adipocytes is progressing substantially in mice. However, much less is known regarding characterization of brown (BAP) and white adipocyte progenitors (WAPs) in humans, highlighting the need for an in vitro model of human adipocyte development. Here, we report a procedure to selectively derive BAP and WAPs from human-induced pluripotent stem cells. Molecular characterization of APs of both phenotypes revealed that BMP4, Hox8, Hoxc9, and HoxA5 genes were specifically expressed in WAPs, whereas expression of PRDM16, Dio2, and Pax3 marked BAPs. We focused on Pax3 and we showed that expression of this transcription factor was enriched in human perirenal white adipose tissue samples expressing UCP1 and in human classical brown fat. Finally, functional experiments indicated that Pax3 was a critical player of human AP fate as its ectopic expression led to convert WAPs into brown-like APs. Together, these data support a model in which Pax3 is a new marker of human BAPs and a molecular mediator of their fate. The findings of this study could lead to new anti-obesity therapies based on the recruitment of APs and constitute a platform for investigating in vitro the developmental origins of human white and brown adipocytes. Stem Cells 2014;32:1459–1467

Published
2014

8. Mycobacterial P1-Type ATPases Mediate Resistance to Zinc Poisoning in Human Macrophages

Author

Paola Ricciardi Castagnoli, Simon J. Waddell, Isabelle Maridonneau-Parini, Pascale Peyron, Sylvain Tilleul, Renaud Poincloux, Ludovic Tailleux, Yannick Poquet, Chantal de Chastellier, Qian Gao, Philip D. Butcher, Florence Levillain, Chuan Wang, Hélène Botella, Olivier Neyrolles, Guillaume M. Charrière, Brigitte Gicquel, Geanncarlo Lugo-Villarino, Irène Brandli, Maria Foti, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Dynamique de la membrane et du cytosquelette, Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Key Laboratory of Medical Molecular Virology - Fudan University, Fudan University [Shanghai], Génétique mycobactérienne - Mycobacterial genetics, Institut Pasteur [Paris] (IP), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Brighton and Sussex Medical School (BSMS), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), St George's, University of London, Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Génétique et biochimie des microorganismes (GBM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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 Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut Pasteur [Paris], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Botella, H, Levillain, F, Poincloux, R, Poquet, Y, Brandli, I, Wang, C, Tailleux, L, Tilleul, S, Charriere, G, Waddel, S, Foti, M, Lugo Villarino, G, Gao, Q, Maridonneau Parini, I, Castagnoli, P, De Chastellier, C, and Neyrolles, O

Subjects
Cancer Research, MESH: Mycobacterium tuberculosis, ATPase, medicine.disease_cause, Q1, MESH: Zinc, Mice, Mycobacterium Tuberculosis, macrophages, Metal poisoning, MESH: Animals, MESH: Tuberculosis, Cells, Cultured, Phagosome, 0303 health sciences, Mice, Inbred BALB C, MED/04 - PATOLOGIA GENERALE, 3. Good health, Zinc, QR180, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Efflux, Intracellular, MESH: Cells, Cultured, MESH: Mice, Inbred BALB C, chemistry.chemical_element, Biology, Microbiology, Article, 03 medical and health sciences, Virology, Immunology and Microbiology(all), MESH: Bacterial Proton-Translocating ATPases, medicine, Animals, Humans, Tuberculosis, MESH: Mice, Molecular Biology, 030304 developmental biology, QR0075, MESH: Humans, 030306 microbiology, Macrophages, MESH: Macrophages, Mycobacterium tuberculosis, chemistry, Cytoplasm, Bacterial Proton-Translocating ATPases, Zinc toxicity, biology.protein, Parasitology, MESH: Female
Abstract

Summary Mycobacterium tuberculosis thrives within macrophages by residing in phagosomes and preventing them from maturing and fusing with lysosomes. A parallel transcriptional survey of intracellular mycobacteria and their host macrophages revealed signatures of heavy metal poisoning. In particular, mycobacterial genes encoding heavy metal efflux P-type ATPases CtpC, CtpG, and CtpV, and host cell metallothioneins and zinc exporter ZnT1, were induced during infection. Consistent with this pattern of gene modulation, we observed a burst of free zinc inside macrophages, and intraphagosomal zinc accumulation within a few hours postinfection. Zinc exposure led to rapid CtpC induction, and ctpC deficiency caused zinc retention within the mycobacterial cytoplasm, leading to impaired intracellular growth of the bacilli. Thus, the use of P1-type ATPases represents a M. tuberculosis strategy to neutralize the toxic effects of zinc in macrophages. We propose that heavy metal toxicity and its counteraction might represent yet another chapter in the host-microbe arms race., Highlights ► Zinc accumulates in the M. tuberculosis (Mtb) phagosome in macrophages (Mϕ) ► Mtb P1-type ATPases, including CtpC, are induced upon exposure to zinc inside Mϕ ► CtpC enables Mtb resistance to zinc poisoning and intracellular survival in Mϕ ► P1-type zinc efflux ATPase ZntA null E. coli is highly susceptible to Mϕ killing

Published
2011
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9. Transplantation of Adipose Tissue-Derived Stromal Cells Increases Mass and Functional Capacity of Damaged Skeletal Muscle

Author

Jonathan Levin, Jean-Paul Micallef, Jean Nouguès, Francis Bacou, Ramzi Boubaker el Andalousi, P.-A. Daussin, Michel Chammas, Louis Casteilla, Yves Reyne, Différenciation Cellulaire et Croissance (DCC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2), Hôpital Lapeyronie, Institut National de la Recherche Agronomique (INRA), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Stromal cell, [SDV]Life Sciences [q-bio], Muscle Fibers, Skeletal, Cell, Cell- and Tissue-Based Therapy, Biomedical Engineering, lcsh:Medicine, Adipose tissue, Cell therapy, 03 medical and health sciences, medicine, Animals, Regeneration, [INFO]Computer Science [cs], Progenitor cell, Muscle, Skeletal, Transplantation, 030102 biochemistry & molecular biology, Chemistry, lcsh:R, Skeletal muscle, Cell Differentiation, Cell Biology, Anatomy, Cell biology, Staining, 030104 developmental biology, medicine.anatomical_structure, Adipose Tissue, Rabbits, Stromal Cells
Abstract

International audience; The regenerating skeletal muscle environment is capable of inducing uncommitted progenitors to terminally differentiate. The aim of this work was to determine whether adipose tissue-derived stromal cells were able to participate in muscle regeneration and to characterize the effect on muscle mass and functional capacities after transplantation of these cells. Adipose tissue stromal cells labeled with Adv cyto LacZ from 3-day-old primary cultures (SVF1) were autotransplanted into damaged tibialis anterior muscles. Fifteen days later, beta-glactosidase staining of regenerated fibers was detected, showing participation of these cells in muscle regeneration. Two months after SVF1 cell transfer, muscles were heavier, showed a significantly larger fiber section area, and developed a significantly higher maximal force compared with damaged control muscles. These results are similar to those previously obtained after satellite cell transplantation. However, SVF1 transfer also generated a small amount of adipose tissue localized along the needle course. To minimize these adipose contaminants, we transferred cells from 7-day-old secondary cultures of the SVF1, containing only a small proportion of already engaged preadipocytes (SVF2). Under these conditions, no adipose tissue was observed in regenerated muscle but there was also no effect on muscle performances compared with damaged control muscles. This result provides further evidence for the existence of progenitor cells in the stromal fraction of freshly isolated adipose tissue cells, which, under our conditions, keep some of their pluripotent properties in primary cultures.

Published
2004

10. α-Galactosidase/Sucrose Kinase (AgaSK), a Novel Bifunctional Enzyme from the Human Microbiome Coupling Galactosidase and Kinase Activities

Author

Laetitia Bruel, Gerlind Sulzenbacher, Marine Cervera Tison, Josette Perrier, Thierry Giardina, Ange Pujol, David Ropartz, Cendrine Nicoletti, Anne Galinier, Michel Fons, Frédérique Pompeo, Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Biopolymers Interact Assemblies (UR1268), Institut National de la Recherche Agronomique (INRA), Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Giardina, Thierry, Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), This work was supported by the CNRS, the Agence Nationale de la Recherche (ANR) contract 'P-loop proteins,' and the 'Ministere de l'Enseignement Superieur.', Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA)

Subjects
Models, Molecular, biochemistry and molecular biology, microbial enzymes, Crystallography, X-Ray, Biochemistry, α-Galactosides, Substrate Specificity, chemistry.chemical_compound, Catalytic Domain, Ruminococcus, Glycoside hydrolase, Anaerobiosis, galactose, sucrose, kinase activity, Raffinose, chemistry.chemical_classification, 0303 health sciences, food and beverages, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Intestines, Phosphotransferases (Alcohol Group Acceptor), kinase, Molecular Sequence Data, Biology, 03 medical and health sciences, Hydrolase, Animals, Humans, Phosphofructokinase 2, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Protein Structure, Quaternary, Melibiose, Molecular Biology, 030304 developmental biology, Alpha-galactosidase, 030306 microbiology, fungi, Cell Biology, Rats, galactosidase, Enzyme, chemistry, carbohydrate, alpha-Galactosidase, Galactose, Enzymology, biology.protein, Metagenome, Protein Multimerization
Abstract

alpha-Cialactosides are non-digestible carbohydrates widely distributed in plants. They are a potential source of energy in our daily food, and their assimilation by microbiota may play a role in obesity. In the intestinal tract, they are degraded by microbial glycosidases, which are often modular enzymes with catalytic domains linked to carbohydrate-binding modules. Here we introduce a bifunctional enzyme from the human intestinal bacterium Ruminococcus gnavus E1, alpha-galactosidase/sucrose kinase (AgaSK). Sequence analysis showed that AgaSK is composed of two domains: one closely related to alpha-galactosidases from glycoside hydrolase family GH36 and the other containing a nucleotide-binding motif. Its biochemical characterization showed that AgaSK is able to hydrolyze melibiose and raffinose to galactose and either glucose or sucrose, respectively, and to specifically p hosphorylate sucrose on the C6 position of glucose in the presence of ATP. The production of sucrose-6-P directly from raffinose points toward a glycolytic pathway in bacteria, not described so far. The crystal structures of the galactosidase domain in the apo form and in complex with the product shed light onto the reaction and substrate recognition mechanisms and highlight an oligorneric state necessary for efficient substrate binding and suggesting a cross-talk between the galactose and kinase domains.

Published
2011

11. Possible common central pathway for resistin and insulin in regulating food intake

Author

Carlo Polidori, Carlo Cifani, Yves Durocher, Maurizio Massi, Philippe Rouet, Atul Pathak, Luc Pénicaud, Fatima Smih, Simon, Marie Francoise, Department of Experimental Medicine and Public Health, Health University of Camerino, Animal Cell Technology Group, Consiglio Nazionale delle Ricerche [Roma] (CNR)-Biotechnologies Research Institute, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, medicine.medical_specialty, food intake, Physiology, medicine.medical_treatment, Adipose tissue, Neuropeptide, Peptide hormone, Biology, Hyperphagia, adipocyte-derived peptides, methods, chemistry.chemical_compound, Internal medicine, Adipocyte, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, Insulin, rat, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Neuropeptide Y, Resistin, Obesity, Rats, Wistar, Pancreatic hormone, Injections, Intraventricular, Dose-Response Relationship, Drug, Animal, Appetite Regulation, Body Weight, Brain, Neuropeptide Y receptor, Rats, Endocrinology, chemistry, Adipose Tissue, Diabetes Mellitus, Type 2, Peptides, Metabolic Networks and Pathways, Biotechnology
Abstract

Aim: Adipose tissue has been the object of intense research in the field of obesity and diabetes diseases in the last decade. Examination of adipocyte-secreted peptides led to the identification of a unique polypeptide, resistin (RSTN), which has been suggested as a link between obesity and diabetes. RSTN plays a clearly documented role in blocking insulin (INS)-induced hypoglycaemia. As brain injection of INS affects feeding behaviour, we studied the possible interaction between INS and RSTN in food-deprived rats, measuring effects on food intake. In addition, we examined how RSTN might affect neuropeptide Y (NPY)-induced feeding, as studies have shown that rat RSTN can interfere with the NPY system. Methods: Overnight food-deprived rats were injected into the third brain ventricle (3V) with either INS (10 or 20 mUI), RSTN (0.1–0.4 nmol/rat), or saline before access to food. Another group of rats was injected into the 3V with RSTN alone, NPY alone or RSTN plus NPY. Their food intake and body weight were measured. Results: Our results confirm the hypophagic effect of RSTN on food deprivation-induced food intake, and more importantly, show that RSTN neither potentiates nor blocks the effects of INS on food intake, but does reduce the hyperphagic effect of NPY. Conclusion: The observation that RSTN does not modify feeding INS-induced hypophagia, but does influence NPY-induced feeding, points to the possibility that RSTN may be involved in control of food intake through an NPY-ergic mechanism as INS.

Published
2009

12. Choosing an Adipose Tissue Depot for Sampling. Factors in selection and depot specificity

Author

Casteilla, Louis, Pénicaud, Luc, Cousin, Béatrice, Calise, Denis, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), CNRS, Toulouse, France, Laboratoire de micro-chirurgie, and Laboratoire de Micro Chirurgie

Subjects
animals, rats, obesity, adipose tissue/anatomy & histology/metabolism/surgery, mice, body fat distribution, adipocytes/cytology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], humans, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, laboratory techniques and procedures
Published
2008

13. Involvement of cholecystokinin 2 receptor in food intake regulation: hyperphagia and increased fat deposition in cholecystokinin 2 receptor-deficient mice

Author

Claude Knauf, Rémy Burcelin, Philippe Valet, Hubert Lulka, Stéphanie Broussaud, Pascal Clerc, Maria Gràcia Coll Constans, Daniel Fourmy, Christian Carpéné, Charlotte Guigné, Catherine Seva, Luc Pénicaud, Stéphane Leung-Theung-Long, Marlène Dufresne, Christophe Perrin, Biologie et Pathologie Digestive, IFR 31 Louis Bugnard (IFR 31), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-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), Animal Facility , Institut Fédératif de Recherche 31, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Unité de recherche sur les obésités, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Simon, Marie Francoise

Subjects
Blood Glucose, Male, Mice, Obese, Cholecystokinin receptor, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Endocrinology, Glucose homeostasis, MESH: Obesity, MESH: Animals, Receptor, MESH: Mice, Obese, Adiposity, Cholecystokinin, Mice, Knockout, 2. Zero hunger, 0303 health sciences, digestive, oral, and skin physiology, MESH: Energy Metabolism, MESH: Motor Activity, Cholecystokinin B receptor, Ghrelin, MESH: Hyperphagia, medicine.drug, medicine.medical_specialty, MESH: Glucose Tolerance Test, Hyperphagia, Motor Activity, Biology, MESH: Receptor, Cholecystokinin B, 03 medical and health sciences, Insulin resistance, MESH: Mice, Inbred C57BL, Orexigenic, Internal medicine, medicine, Animals, Obesity, MESH: Mice, 030304 developmental biology, MESH: Adiposity, Appetite Regulation, Body Weight, Glucose Tolerance Test, medicine.disease, Receptor, Cholecystokinin B, MESH: Male, MESH: Body Weight, Mice, Inbred C57BL, MESH: Blood Glucose, Energy Metabolism, 030217 neurology & neurosurgery, MESH: Appetite Regulation
Abstract

International audience; The role of cholecystokinin (CCK) as a satiety factor has been extensively documented. Although most work implies that CCK1 receptor mediates the control of food intake, a contributing role for CCK2 receptor (CCK2R) in the CCK-induced satiety cannot be totally excluded. The hypothesis that CCK2R invalidation disrupts regulatory pathways with impact on feeding behavior was examined in CCK2R(-/-) mice. CCK2R(-/-) mice developed obesity that was associated with hyperphagia. Obesity was related with increased fat deposition resulting from adipocyte hypertrophy. Expression of several adipokines was dysregulated consistently with obesity. Moreover, obesity was associated with disturbed glucose homeostasis as revealed by increased fasting glycemia and insulinemia, impaired glucose tolerance, and hepatic insulin resistance in CCK2R(-/-) mice. In vitro analysis of isolated adipocytes metabolism was consistent with increased storage but preserved insulin sensitivity. Suppression of feeding and concomitant increased expression of hypothalamic proopiomelanocortin after intracerebroventricular injection of gastrin into control mice demonstrates that hypothalamic CCK2 receptors mediate inhibition of food intake. Comparative analysis of hypothalamic mediator gene expression in fed knockout and control mice demonstrated overexpression of ghrelin receptors in CCK2R(-/-) mice, indicating up-regulation of orexigenic pathways. This effect was also observed after body weight normalization, indicating a causative role in the development of hyperphagia and obesity of CCK2R(-/-) mice. Our results give evidence that CCK2 receptor activity plays a contributing regulatory role in the control of food intake.

Published
2007

14. Adipose tissue-derived cells: from physiology to regenerative medicine

Author

Christian Dani, Louis Casteilla, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)

Subjects
MESH: Cell Differentiation, medicine.medical_specialty, Stromal cell, MESH: Myocardium, Endocrinology, Diabetes and Metabolism, MESH: Neurons, Adipokine, Adipose tissue, MESH: Stem Cells, Biology, Regenerative medicine, MESH: Adipose Tissue, Brown, MESH: Hematopoietic Stem Cells, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Adipose Tissue, Brown, Internal medicine, Adipocyte, Internal Medicine, medicine, Animals, Humans, Regeneration, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Muscle, Skeletal, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Neurons, 0303 health sciences, MESH: Muscle, Skeletal, MESH: Humans, Myocardium, Stem Cells, Leptin, Regeneration (biology), MESH: Regeneration, Cell Differentiation, General Medicine, Hematopoietic Stem Cells, 3. Good health, Adipose Tissue, chemistry, 030220 oncology & carcinogenesis, Stem cell, MESH: Adipose Tissue
Abstract

International audience; During the last past years, the importance and the role of adipose tissues have been greatly expanded. After finding that adipose tissues are metabolically very active, the discovery of leptin moved the status of adipose tissue towards an endocrine tissue able to interact with all major organs via secretion of adipokines. Some years ago, the presence of adipocyte precursors, termed preadipocytes, has been described in all adipose tissue depots from various species of different age. More recently, the discovery that different phenotypes can be obtained from stroma cells of adipose tissue has largely emphazised the concept of adipose tissue plasticity. Therefore, raising great hope in regenerative medicine as adipose tissue can be easily harvested in adults it could represent an abundant source of therapeutic cells. Thus, adipose tissue plays the dual role of Mr Obese Hyde as a main actor of obesity and of Dr Regenerative Jekyll as a source of therapeutic cells. Adipose tissue has not yet revealed all its mysteries although one facet could not be well understood without the other one.

Published
2006

15. Macrophage characteristics of stem cells revealed by transcriptome profiling

Author

Louis Casteilla, Mireille André, Christian Dani, Corinne Saillan-Barreau, Emmanuelle Arnaud, Guillaume M. Charrière, Béatrice Cousin, Luc Pénicaud, Ali Massoudi, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)

Subjects
Male, Transcription, Genetic, MESH: Algorithms, MESH: Flow Cytometry, MESH: Stem Cells, Cell Separation, Biology, Stem cell marker, MESH: Cell Separation, Transcriptome, MESH: Gene Expression Profiling, 03 medical and health sciences, Mice, 0302 clinical medicine, Phagocytosis, MESH: Mice, Inbred C57BL, MESH: Microscopy, Confocal, Animals, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Progenitor cell, MESH: Phagocytosis, MESH: Mice, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Microscopy, Confocal, Microarray analysis techniques, MESH: Transcription, Genetic, Gene Expression Profiling, Stem Cells, MESH: Embryo, Mammalian, Cell Biology, Embryo, Mammalian, Flow Cytometry, Phenotype, Embryonic stem cell, MESH: Male, Cell biology, Gene expression profiling, Mice, Inbred C57BL, Macrophages, Peritoneal, Stem cell, MESH: Macrophages, Peritoneal, 030217 neurology & neurosurgery, Algorithms, MESH: Cells, Cultured
Abstract

International audience; We previously showed that the phenotypes of adipocyte progenitors and macrophages were close. Using functional analyses and microarray technology, we first tested whether this intriguing relationship was specific to adipocyte progenitors or could be shared with other progenitors. Measurements of phagocytic activity and gene profiling analysis of different progenitor cells revealed that the latter hypothesis should be retained. These results encouraged us to pursue and to confirm our analysis with a gold-standard stem cell population, embryonic stem cells or ESC. The transcriptomic profiles of ESC and macrophages were clustered together, unlike differentiated ESC. In addition, undifferentiated ESC displayed higher phagocytic activity than other progenitors, and they could phagocytoze apoptotic bodies. These data suggest that progenitors and stem cells share some characteristics of macrophages. This opens new perspectives on understanding stem cell phenotype and functionalities such as a putative role of stem cells in tissue remodeling by discarding dead cells but also their immunomodulation or fusion properties.

Published
2006

16. A new ATP-sensitive K+ channel-independent mechanism is involved in glucose-excited neurons of mouse arcuate nucleus

Author

Luc Pénicaud, Anne Taupignon, Anne Lorsignol, Xavier Fioramonti, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Physiologie et physiopathologie de la signalisation cellulaire (PPSC), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Patch-Clamp Techniques, Endocrinology, Diabetes and Metabolism, Cesium, Membrane Potentials, ventromedial hypothalamus, Mice, chemistry.chemical_compound, 0302 clinical medicine, arcuate nucleus, HGE, tetrodotoxin, Mice, Knockout, Neurons, 0303 health sciences, Arc (protein), ventromedian nucleus, KATP channel, HGI, Depolarization, ARC, Potassium channel, 3. Good health, medicine.anatomical_structure, Tetrodotoxin, medicine.medical_specialty, ATP-sensitive K+ channel, In Vitro Techniques, Biology, TTX, 03 medical and health sciences, Chlorides, Arcuate nucleus, high glucose excited, Internal medicine, high glucose inhibited, Internal Medicine, medicine, Animals, Patch clamp, Potassium Channels, Inwardly Rectifying, 030304 developmental biology, Arcuate Nucleus of Hypothalamus, VMN, VMH, Glucose, Endocrinology, chemistry, Biophysics, Neuron, Nucleus, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

International audience; Glucose is known to modify electrical activity of neurons in different hypothalamic areas such as the arcuate nucleus (ARC) or the ventromedian nucleus. In these structures, it has been demonstrated that glucose-induced excitation of neurons involves ATP-sensitive K(+) (K(ATP)) channel closure. The aim of the present study was to determine whether ARC neurons were able to detect high extracellular glucose concentrations and which mechanisms were involved in this detection by using whole-cell and cell-attached patch-clamp techniques in acute mouse brain slices. An increase from 5 to 20 mmol/l glucose stimulated 19% and inhibited 9% of ARC neurons. Because of the high-glucose concentrations used, we called these neurons high-glucose-excited (HGE) and high-glucose-inhibited (HGI) neurons, respectively. Glucose-induced depolarization of HGE neurons was not abolished by tetrodotoxin treatment and was correlated with an increase of membrane conductance that reversed at approximately 20 mV. Experiments with diazoxide, pinacidil, or tolbutamide showed that K(ATP) channels were present and functional in most of the ARC neurons but were mostly closed at 5 mmol/l glucose. Moreover, HGE neurons were also present in ARC of Kir6.2 null mice. These results suggested that ARC neurons have the ability to sense higher glucose concentrations than 5 mmol/l through a new K(ATP) channel-independent mechanism.

Published
2004

17. Effect of the new imidazoline derivative S-22068 (PMS 847) on insulin secretion in vitro and glucose turnover in vivo in rats

Author

Beatrice Guardiola-Lemaitre, Susan L.F. Chan, Agnès Pelé-Tounian, Dominique Manechez, Frédéric Rondu, Noel G. Morgan, Azzdine Lamouri, Estera Touboul, Alain Ktorza, Marie-Hélène Giroix, Luc Pénicaud, Jean-Jacques Godfroid, Bruno Pfeiffer, Pierre Renard, Gaëlle Le Bihan, Institut de Recherches Servier, SERVIER, Les Laboratoires SERVIER, Institut de Recherche Servier, Institut de Recherches Internationales Servier (IRIS-Servier), Centre National de la Recherche Scientifique (CNRS), Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiopathologie de la nutrition (LPN), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Imidazoline receptor, In Vitro Techniques, Carbohydrate metabolism, Biology, Piperazines, Diabetes Mellitus, Experimental, Islets of Langerhans, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Insulin Secretion, medicine, Diazoxide, Animals, Hypoglycemic Agents, Insulin, Rats, Wistar, Antihypertensive Agents, Pancreatic hormone, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, 0303 health sciences, Imidazoles, medicine.disease, Rats, Rats, Zucker, Glucose, Endocrinology, Liver, L-Glucose, chemistry, Basal (medicine), Glucose Clamp Technique, Rubidium Radioisotopes, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, medicine.drug
Abstract

We have investigated the possible mechanisms underlying the antihyperglycaemic effect of the imidazoline derivative S-22068. In vitro, in the presence of 5 mmol/l glucose, S-22068 (100 micromol/l) induced a significant and sustained increase in insulin secretion from isolated, perifused, rat islets and a marked sensitization to a subsequent glucose challenge (10 mmol/l). S-22068 (100 micromol/l was able to antagonize the stimulatory effect of diazoxide on 86Rb efflux from preloaded islets incubated in the presence of 20 mmol/l glucose. Experiments were also performed to investigate whether S-22068 can alter glucose turnover and peripheral insulin sensitivity in vivo in mildly diabetic rats and obese, insulin resistant, Zucker rats. Neither glucose production nor individual tissue glucose utilization was modified by S-22068 in either group of rats. Similar results were obtained whether the studies were performed under basal conditions or during euglycaemic/hyperinsulinemic clamps. The results suggest that S-22068 exerts part of its antihyperglycaemic effect by promoting insulin secretion without alteration of peripheral insulin sensitivity.

Published
1999

18. Evidence for numerous brown adipocytes lacking functional beta 3-adrenoceptors in fat pads from nonhuman primates

Author

Daniel Ricquier, Louis Casteilla, Alain Bousquet-Mélou, N. Viguerie-Bascands, M Berlan, J Galitzky, Dominique Larrouy, Neurobiologie, plasticité tissulaire et métabolisme énergétique (NPTME), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, White adipose tissue, MESH: Base Sequence, Polymerase Chain Reaction, Biochemistry, Ion Channels, chemistry.chemical_compound, Endocrinology, Adipose Tissue, Brown, Adipocyte, Brown adipose tissue, MESH: Animals, Uncoupling Protein 1, MESH: Papio, 0303 health sciences, 030302 biochemistry & molecular biology, MESH: Mitochondrial Proteins, Thermogenin, medicine.anatomical_structure, Female, MESH: Membrane Proteins, Beta-3 adrenergic receptor, medicine.medical_specialty, Lipolysis, Blotting, Western, Molecular Sequence Data, MESH: Receptors, Adrenergic, beta, MESH: Carrier Proteins, Biology, MESH: Adipose Tissue, Brown, Mitochondrial Proteins, 03 medical and health sciences, Internal medicine, Receptors, Adrenergic, beta, medicine, Animals, MESH: Blotting, Western, MESH: Lipolysis, RNA, Messenger, Beta (finance), 030304 developmental biology, MESH: RNA, Messenger, MESH: Molecular Sequence Data, Base Sequence, Biochemistry (medical), Membrane Proteins, MESH: Polymerase Chain Reaction, MESH: Male, chemistry, Receptors, Adrenergic, beta-3, MESH: Ion Channels, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Carrier Proteins, MESH: Receptors, Adrenergic, beta-3, MESH: Female, Papio
Abstract

International audience; Brown adipose tissue (BAT) is involved in the control of energy balance and has been demonstrated to be activated through beta 3-adrenoceptor (beta 3-AR) occupation in rodents. The ability to specifically activate energy expenditure via this receptor is of great interest for the treatment of obesity. Nevertheless, the extent of BAT and the presence of a functional beta 3-AR in humans are now debated, and this situation is difficult to clarify for evident practical and ethical reasons. We investigated the occurrence of brown adipocytes in fat deposits of prepubertal baboons using antibodies raised against uncoupling protein (UCP) in Western blotting and immunocytology experiments. UCP was detected in all types of fat pads studied and was revealed in multilocular cells. Pericardiac and axillary adipose tissues displayed large amounts of UCP and can be assimilated to typical BAT. Most of the other pads looked like white adipose tissue, but exhibited areas with clusters of brown adipocytes and, thus, can be assimilated to the convertible adipose tissue as previously described in rodents. The presence of beta 3-ARs was evaluated by both beta 2-agonist-stimulated lipolysis and messenger ribonucleic acid (mRNA) expression studies. There was no significant lipolytic effect of any of the beta 3-AR agonists tested (SR 58611A, BRL 37344, CGP 12177, or CL 316243) in either white or brown tissues. PCR analysis demonstrated that beta 3-AR mRNA expression is not related to the UCP content of fat pads and that beta 3-AR expression is low. This study demonstrates the presence of great proportions of brown adipocytes in adipose tissue and the heterogeneity of the fat pads in baboons. The lack of a metabolic effect of beta 3-agonists combined with the weak expression of beta 3-AR mRNAs raise the question of the role of beta 3-ARs in adipose tissues of primates.

Published
1996

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