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1. Protocol for the preclinical evaluation of gut barrier function and immune interaction in an HT-29/PBMC co-culture model

Author: Gwendoline Astre, Laurianne Créchet, Nicolas Pomié, Ophélie Pereira, Patrice D. Cani, Claude Knauf, and Anne Abot
Subjects: cell culture, health sciences, immunology, Science (General), Q1-390
Abstract: Summary: Here, we present a protocol for the pre-clinical evaluation of gut barrier function and immune interaction in an HT-29/PBMC co-culture model. We describe steps for culturing HT-29 cells and peripheral blood mononuclear cells (PBMCs), assembling the co-culture model, and testing cell viability. We then detail procedures for performing efficacy tests through stress challenges and barrier permeability assays.For complete details on the use and execution of this protocol, please refer to Abot et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Published: 2024
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2. Effect of the dietary supplement PERMEAPROTECT+ TOLERANCE© on gut permeability in a human co-culture epithelial and immune cells model

Author: Anne Abot, Nicolas Pomié, Gwendoline Astre, Patrice D. Cani, Justine Aussant, Emmanuel Barrat, and Claude Knauf
Subjects: Intestinal permeability, Epithelial cells, Immune cells, Antioxidant, Science (General), Q1-390, Social sciences (General), H1-99
Abstract: Background and objective: The leaky gut syndrome is characterized by an intestinal hyperpermeability observed in multiple chronic disorders. Alterations of the gut barrier are associated with translocation of bacterial components increasing inflammation, oxidative stress and eventually dysfunctions of cellular interactions at the origin pathologies. Therapeutic and/or preventive approaches have to focus on the identification of novel targets to improve gut homeostasis. In this context, this study aims to identify the role of PERMEAPROTECT + TOLERANE©, known as PERMEA, a food complement composed of a combination of factors (including l-Glutamine) known to improve gut physiology. Methods: We tested the effects of PERMEA or l-Glutamine alone (as reference) on gut permeability (FITC dextran method, expression of tight junctions) and its inflammatory/oxidative consequences (cytokines and redox assays, RT-qPCR) in a co-culture of human cells (peripheral blood mononuclear cells and intestinal epithelial cells) challenged with TNFα. Results: PERMEA prevented intestinal hyperpermeability induced by inflammation. This was linked with its antioxidant and immunomodulatory properties showing a better efficacity than l-Glutamine alone on several parameters including permeability, global antioxidant charge and production of cytokines. Conclusion: PERMEA is more efficient to restore intestinal physiology, reinforcing the concept that combination of food constituents could be used to prevent the development of numerous diseases.
Published: 2024
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3. Proenkephalin deletion in hematopoietic cells induces intestinal barrier failure resulting in clinical feature similarities with irritable bowel syndrome in mice

Author: Xavier Mas-Orea, Lea Rey, Louise Battut, Cyrielle Bories, Camille Petitfils, Anne Abot, Nadine Gheziel, Eve Wemelle, Catherine Blanpied, Jean-Paul Motta, Claude Knauf, Frederick Barreau, Eric Espinosa, Meryem Aloulou, Nicolas Cenac, Matteo Serino, Lionel Mouledous, Nicolas Fazilleau, and Gilles Dietrich
Subjects: Biology (General), QH301-705.5
Abstract: Abstract Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammation-induced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions. Here, we show that chimeric mice engrafted with enkephalin-deficient bone marrow cells exhibit not only visceral hypersensitivity but also an increase in both epithelial paracellular and transcellular permeability, an alteration of the microbial topography resulting in increased bacteria-epithelium interactions and a higher frequency of IgA-producing plasma cells in Peyer’s patches. All these alterations of the intestinal homeostasis are associated with an anxiety-like behavior despite the absence of an overt inflammation as observed in patients with irritable bowel syndrome. Thus, our results show that immune cell-derived enkephalins play a pivotal role in maintaining gut homeostasis and normal behavior in mice. Because a defect in the mucosal opioid system remarkably mimics some major clinical symptoms of the irritable bowel syndrome, its identification might help to stratify subgroups of patients.
Published: 2023
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4. Pasteurized Akkermansia muciniphila improves glucose metabolism is linked with increased hypothalamic nitric oxide release

Author: Anne Abot, Amandine Brochot, Nicolas Pomié, Gwendoline Astre, Céline Druart, Willem M. de Vos, Claude Knauf, and Patrice D. Cani
Subjects: Paraprobiotics, Enteric nervous system, Gut-brain axis, Diabetes, Science (General), Q1-390, Social sciences (General), H1-99
Abstract: Background and objective: Pasteurized Akkermansia muciniphila cells have shown anti-diabetic effects in rodents and human. Although, its primary site of action consists in maintaining the gut barrier function, there are no study exploring if A. muciniphila controls glycemia via a gut to brain axis. Targeting the gut motility represents an alternative pathway to treat hyperglycemia. Here, we tested the impact of pasteurized A. muciniphila on gut motility, gut-brain axis and glucose metabolism. Methods: We used mice fed a 45% high-fat (HFD) treated or not with pasteurized A. muciniphila MucT during 12 weeks. We measured the effects of the treatment on body weight gain, glucose metabolism (insulin, glycemia, glucose tolerance), gut contraction and enteric neurotransmitter release, and hypothalamic nitric oxide (NO) release. Results: We show that pasteurized A. muciniphila exerts positive effects on different metabolic parameters such as body weight, fat mass, insulin, glycemia and glucose tolerance. This could be explained by the ability of pasteurized A. muciniphila supplementation to decrease duodenal contraction and to increase hypothalamic NO release in HFD mice. Conclusion: We demonstrate a novel mode of action of pasteurized A. muciniphila explaining its beneficial impact on the control of glycemia in a preclinical model of type 2 diabetes via gut-brain axis signaling.
Published: 2023
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5. Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in parasite/host interaction[S]

Author: Lucie Paloque, Teresa Perez-Berezo, Anne Abot, Jessica Dalloux-Chioccioli, Sandra Bourgeade-Delmas, Pauline Le Faouder, Julien Pujo, Marie-Ange Teste, Jean-Marie François, Nils Helge Schebb, Malwina Mainka, Corinne Rolland, Catherine Blanpied, Gilles Dietrich, Justine Bertrand-Michel, Céline Deraison, Alexis Valentin, and Nicolas Cenac
Subjects: cytochrome P450, infection, macrophages, ω-3, metabolism, arachidonic acid, Biochemistry, QD415-436
Abstract: Inside the human host, Leishmania infection starts with phagocytosis of infective promastigotes by macrophages. In order to survive, Leishmania has developed several strategies to manipulate macrophage functions. Among these strategies, Leishmania as a source of bioactive lipids has been poorly explored. Herein, we assessed the biosynthesis of polyunsaturated fatty acid metabolites by infective and noninfective stages of Leishmania and further explored the role of these metabolites in macrophage polarization. The concentration of docosahexaenoic acid metabolites, precursors of proresolving lipid mediators, was increased in the infective stage of the parasite compared with the noninfective stage, and cytochrome P450-like proteins were shown to be implicated in the biosynthesis of these metabolites. The treatment of macrophages with lipids extracted from the infective forms of the parasite led to M2 macrophage polarization and blocked the differentiation into the M1 phenotype induced by IFN-γ. In conclusion, Leishmania polyunsaturated fatty acid metabolites, produced by cytochrome P450-like protein activity, are implicated in parasite/host interactions by promoting the polarization of macrophages into a proresolving M2 phenotype.
Published: 2019
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6. Glucose Stimulates Gut Motility in Fasted and Fed Conditions: Potential Involvement of a Nitric Oxide Pathway

Author: Eve Wemelle, Lionel Carneiro, Anne Abot, Jean Lesage, Patrice D. Cani, and Claude Knauf
Subjects: gut motility, glucose, enterosynes, NO, glucose transporters, type 2 diabetes, Nutrition. Foods and food supply, TX341-641
Abstract: (1) Background: Type 2 diabetes (T2D) is associated with a duodenal hypermotility in postprandial conditions that favors hyperglycemia and insulin resistance via the gut-brain axis. Enterosynes, molecules produced within the gut with effects on the enteric nervous system, have been recently discovered and pointed to as potential key modulators of the glycemia. Indeed, targeting the enteric nervous system that controls gut motility is now considered as an innovative therapeutic way in T2D to limit intestinal glucose absorption and restore the gut-brain axis to improve insulin sensitivity. So far, little is known about the role of glucose on duodenal contraction in fasted and fed states in normal and diabetic conditions. The aim of the present study was thus to investigate these effects in adult mice. (2) Methods: Gene-expression level of glucose transporters (SGLT-1 and GLUT2) were quantified in the duodenum and jejunum of normal and diabetic mice fed with an HFD. The effect of glucose at different concentrations on duodenal and jejunal motility was studied ex vivo using an isotonic sensor in fasted and fed conditions in both normal chow and HFD mice. (3) Results: Both SGLT1 and GLUT2 expressions were increased in the duodenum (47 and 300%, respectively) and jejunum (75% for GLUT2) of T2D mice. We observed that glucose stimulates intestinal motility in fasted (200%) and fed (400%) control mice via GLUT2 by decreasing enteric nitric oxide release (by 600%), a neurotransmitter that inhibits gut contractions. This effect was not observed in diabetic mice, suggesting that glucose sensing and mechanosensing are altered during T2D. (4) Conclusions: Glucose acts as an enterosyne to control intestinal motility and glucose absorption through the enteric nervous system. Our data demonstrate that GLUT2 and a reduction of NO production could both be involved in this stimulatory contracting effect.
Published: 2022
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7. Camu-Camu Reduces Obesity and Improves Diabetic Profiles of Obese and Diabetic Mice: A Dose-Ranging Study

Author: Anne Abot, Amandine Brochot, Nicolas Pomié, Eve Wemelle, Céline Druart, Marion Régnier, Nathalie M. Delzenne, Willem M. de Vos, Claude Knauf, and Patrice D. Cani
Subjects: Camu-Camu extract, nutraceuticals, obesity, diabetes, antioxidant, Microbiology, QR1-502
Abstract: Overweight, obesity, and their comorbidities are currently considered a major public health concern. Today considerable efforts are still needed to develop efficient strategies able to attenuate the burden of these diseases. Nutritional interventions, some with plant extracts, present promising health benefits. In this study, we evaluated the action of Camu-Camu (Myrciaria dubia), an Amazonian fruit rich in polyphenols and vitamin C, on the prevention of obesity and associated disorders in mice and the abundance of Akkermansia muciniphila in both cecum and feces. Methods: We investigated the dose-response effects of Camu-Camu extract (CCE) in the context of high-fat-diet (HFD)-induced obesity. After 5 weeks of supplementation, we demonstrated that the two doses of CCE differently improved glucose and lipid homeostasis. The lowest CCE dose (62.5 mg/kg) preferentially decreased non-HDL cholesterol and free fatty acids (FFA) and increased the abundance of A. muciniphila without affecting liver metabolism, while only the highest dose of CCE (200 mg/kg) prevented excessive body weight gain, fat mass gain, and hepatic steatosis. Both doses decreased fasting hyperglycemia induced by HFD. In conclusion, the use of plant extracts, and particularly CCE, may represent an additional option in the support of weight management strategies and glucose homeostasis alteration by mechanisms likely independent from the modulation of A. muciniphila abundance.
Published: 2022
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8. Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons

Author: Anne Abot, Alexandre Lucas, Tereza Bautzova, Arnaud Bessac, Audren Fournel, Sophie Le-Gonidec, Philippe Valet, Cédric Moro, Patrice D. Cani, and Claude Knauf
Subjects: Internal medicine, RC31-1245
Abstract: Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut–brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism) were assessed. Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin. Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D. Keywords: Galanin, Enteric nervous system, Diabetes
Published: 2018
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9. Central Effects of Beta-Blockers May Be Due to Nitric Oxide and Hydrogen Peroxide Release Independently of Their Ability to Cross the Blood-Brain Barrier

Author: Claire Laurens, Anne Abot, Alain Delarue, and Claude Knauf
Subjects: beta-blockers, propranolol, blood-brain barrier, infantile hemangioma, reactive oxygen species, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Propranolol is the first-line treatment for infants suffering from infantile hemangioma. Recently, some authors raised the question of potential neurologic side effects of propranolol due to its lipophilic nature and thus its ability to passively cross the blood-brain barrier (BBB) and accumulate into the brain. Hydrophilic beta-blockers, such as atenolol and nadolol, where therefore introduced in clinical practice. In addition to their classical mode of action in the brain, circulating factors may modulate the release of reactive oxygen/nitrogen species (ROS/RNS) from endothelial cells that compose the BBB without entering the brain. Due to their high capacity to diffuse across membranes, ROS/RNS can reach neurons and modify their activity. The aim of this study was to investigate other mechanisms of actions in which these molecules may display a central effect without actually crossing the BBB. We first performed an oral treatment in mice to measure the accumulation of propranolol, atenolol and nadolol in different brain regions in vivo. We then evaluated the ability of these molecules to induce the release of nitric oxide (NO) and hydrogen peroxide (H2O2) ex vivo in the hypothalamus. As expected, propranolol is able to cross the BBB and is found in brain tissue in higher amounts than atenolol and nadolol. However, all of these beta-blockers are able to induce the secretion of signaling molecules (i.e., NO and/or H2O2) in the hypothalamus, independently of their ability to cross the BBB, deciphering a new potential deleterious impact of hydrophilic beta-blockers in the brain.
Published: 2019
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10. Impact of Intestinal Peptides on the Enteric Nervous System: Novel Approaches to Control Glucose Metabolism and Food Intake

Author: Anne Abot, Patrice D. Cani, and Claude Knauf
Subjects: enteric nervous system, bioactive peptides, food intake, glucose metabolism, diabetes, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: The gut is one of the most important sources of bioactive peptides in the body. In addition to their direct actions in the brain and/or peripheral tissues, the intestinal peptides can also have an impact on enteric nervous neurons. By modifying the endogenousproduction of these peptides, one may expect modify the “local” physiology such as glucose absorption, but also could have a “global” action via the gut–brain axis. Due to the various origins of gut peptides (i.e., nutrients, intestinal wall, gut microbiota) and the heterogeneity of enteric neurons population, the potential physiological parameters control by the interaction between the two partners are multiple. In this review, we will exclusively focus on the role of enteric nervous system as a potential target of gut peptides to control glucose metabolism and food intake. Potential therapeutic strategies based on per os administration of gut peptides to treat type 2 diabetes will be described.
Published: 2018
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11. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation

Author: Anne Abot, Coralie Fontaine, Mélissa Buscato, Romain Solinhac, Gilles Flouriot, Aurélie Fabre, Anne Drougard, Shyamala Rajan, Muriel Laine, Alain Milon, Isabelle Muller, Daniel Henrion, Marine Adlanmerini, Marie‐Cécile Valéra, Anne Gompel, Céline Gerard, Christel Péqueux, Mélanie Mestdagt, Isabelle Raymond‐Letron, Claude Knauf, François Ferriere, Philippe Valet, Pierre Gourdy, Benita S Katzenellenbogen, John A Katzenellenbogen, Françoise Lenfant, Geoffrey L Greene, Jean‐Michel Foidart, and Jean‐François Arnal
Subjects: endothelium, estetrol, estrogen receptor, uterus, Medicine (General), R5-920, Genetics, QH426-470
Abstract: Abstract Estetrol (E4) is a natural estrogen with a long half‐life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand‐binding domain bound to 17β‐estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF‐1 and AF‐2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane‐initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS‐dependent effects in endothelium but also in MCF‐7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.
Published: 2014
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12. PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing

Author: Domagoj Cikes, Kareem Elsayad, Erdinc Sezgin, Erika Koitai, Ferenc Torma, Michael Orthofer, Rebecca Yarwood, Leonhard X. Heinz, Vitaly Sedlyarov, Nasser Darwish Miranda, Adrian Taylor, Sophie Grapentine, Fathiya al-Murshedi, Anne Abot, Adelheid Weidinger, Candice Kutchukian, Colline Sanchez, Shane J. F. Cronin, Maria Novatchkova, Anoop Kavirayani, Thomas Schuetz, Bernhard Haubner, Lisa Haas, Astrid Hagelkruys, Suzanne Jackowski, Andrey V. Kozlov, Vincent Jacquemond, Claude Knauf, Giulio Superti-Furga, Eric Rullman, Thomas Gustafsson, John McDermot, Martin Lowe, Zsolt Radak, Jeffrey S. Chamberlain, Marica Bakovic, Siddharth Banka, and Josef M. Penninger
Subjects: Physiology (medical), Endocrinology, Diabetes and Metabolism, Internal Medicine, Cell Biology
Published: 2023

13. How does apelin affect LH levels? An investigation at the level of GnRH and KNDy neurons

Author: Anne Abot, Vincent Robert, Renaud Fleurot, Hugues Dardente, Vincent Hellier, Pascal Froment, Anne Duittoz, Claude Knauf, and Laurence Dufourny
Subjects: Male, Neurons, Apelin Receptors, Kisspeptins, Neurokinin B, Colforsin, Arcuate Nucleus of Hypothalamus, Luteinizing Hormone, Biochemistry, Dynorphins, Rats, Gonadotropin-Releasing Hormone, Mice, Endocrinology, Animals, Apelin, Steroids, Molecular Biology
Abstract: Hypothalamic control of reproduction relies on GnRH and kisspeptin (KP) secretions. KP neurons are sensitive to sex steroids and metabolic status and their distribution overlaps with neurons producing apelin, a metabolic hormone known to decrease LH secretion in rats. Here, we observed neuroanatomical contacts between apelin fibers and both KP and GnRH neurons in the hypothalamus of male rodents. Intracerebroventricular apelin infusion for 2 weeks in male mice did not decrease LH levels nor did it affect gene expression for KP, neurokinin B and dynorphin. Finally, increasing apelin concentrations did not modulate Ca
Published: 2022

14. Reactive Oxygen Species/Reactive Nitrogen Species as Messengers in the Gut: Impact on Physiology and Metabolic Disorders

Author: Patrice D. Cani, Steven Fried, Anne Abot, Claude Knauf, and UCL - SSS/LDRI - Louvain Drug Research Institute
Subjects: Physiology, Nitrogen, Clinical Biochemistry, chemistry.chemical_element, Inflammation, Oxidative phosphorylation, Type 2 diabetes, Pharmacology, Biochemistry, Redox, Oxygen, chemistry.chemical_compound, medicine, Humans, In patient, Obesity, Molecular Biology, Reactive nitrogen species, General Environmental Science, chemistry.chemical_classification, Reactive oxygen species, Chemistry, Cell Biology, medicine.disease, Reactive Nitrogen Species, Diabetes Mellitus, Type 2, General Earth and Planetary Sciences, medicine.symptom, Reactive Oxygen Species
Abstract: SIGNIFICANCE: The role of reactive oxygen/nitrogen species as "friend" or "foe" messengers in the whole body is well characterized. Depending on the concentration in the tissue considered, these molecular actors exert beneficial or deleterious impacts leading to a pathological state, as observed in metabolic disorders such as type 2 diabetes and obesity. RECENT ADVANCES: Among the tissues impacted by oxidation and inflammation in this pathological state, the intestine is a site of dysfunction that can establish diabetic symptoms, such as alterations in the intestinal barrier, gut motility, microbiota composition, and gut/brain axis communication. In the intestine, reactive oxygen/nitrogen species (from the host and/or microbiota) are key factors that modulate the transition from physiological to pathological signaling. CRITICAL ISSUES: Controlling the levels of intestinal reactive oxygen/nitrogen species is a complicated balance between positive and negative impacts that is in constant equilibrium. Here, we describe the synthesis and degradation of intestinal reactive oxygen/nitrogen species and their interactions with the host. The development of novel redox-based therapeutics that alter these processes could restore intestinal health in patients with metabolic disorders. FUTURE DIRECTIONS: Deciphering the mode of action of reactive oxygen/nitrogen species in the gut of obese/diabetic patients could result in a future therapeutic strategy that combines nutritional and pharmacological approaches. Consequently, preventive and curative treatments must take into account one of the first sites of oxidative and inflammatory dysfunctions in the body, that is, the intestine.
Published: 2021

15. Identification of new enterosynes using prebiotics: roles of bioactive lipids and mu-opioid receptor signalling in humans and mice

Author: Giulio G. Muccioli, Adrien Paquot, Claire Laurens, Alexandre Lucas, Amandine Everard, Etienne Meunier, Cedric Moro, Christophe Fremez, Patrice D. Cani, Arnaud Bessac, Nicolas Pomie, Deborah Carper, Claude Knauf, Jean Lesage, Maxime Fontanie, Eve Wemelle, Xavier Mas Orea, Anne Abot, Gilles Dietrich, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Enterosys, NeuroMicrobiota, Université Catholique de Louvain = Catholic University of Louvain (UCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Centre National d’Études Spatiales [Paris] (CNES), Université de Strasbourg (UNISTRA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie et de biologie structurale (IPBS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Lille - Faculté des Humanités (Lille Humanités), Université de Lille, FRS-FNRS (Fonds de la Recherche Scientifique), UCL - SSS/LDRI - Louvain Drug Research Institute, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Associated Laboratory NeuroMicrobiota (INSERM/UCL), Université Fédérale Toulouse Midi-Pyrénées-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), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Lille - UFR des Humanités (Lille UFRH), SEGUIN, Nathalie, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Blood Glucose, Male, Enkephalin, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_treatment, Receptors, Opioid, mu, Oligosaccharides, Nitric Oxide Synthase Type I, Pharmacology, Gut flora, Enteric Nervous System, Mice, 0302 clinical medicine, enteric nervous system, Brain-Gut Axis, 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid, Gut Microbiota, Receptor, Neurons, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Gastroenterology, Enkephalins, Middle Aged, Hedgehog signaling pathway, 3. Good health, Proenkephalin, diabetes mellitus, prebiotic, motility disorders, μ-opioid receptor, Signal Transduction, Adult, Duodenum, 030209 endocrinology & metabolism, Biology, Diabetes Mellitus, Experimental, lipids, 03 medical and health sciences, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Isotonic Contraction, RNA, Messenger, Protein Precursors, Aged, Prebiotic, Muscle, Smooth, Glucose Tolerance Test, biology.organism_classification, Gastrointestinal Microbiome, PPAR gamma, 030104 developmental biology, Prebiotics, Diabetes Mellitus, Type 2, Enteric nervous system, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectiveThe enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes. The discovery of intestinal actors, such as enterosynes, able to modulate the ENS-induced duodenal contraction is considered an innovative approach. Among all the intestinal factors, the understanding of the role of gut microbes in controlling glycaemia is still developed. We studied whether the modulation of gut microbiota by prebiotics could permit the identification of novel enterosynes.DesignWe measured the effects of prebiotics on the production of bioactive lipids in the intestine and tested the identified lipid on ENS-induced contraction and glucose metabolism. Then, we studied the signalling pathways involved and compared the results obtained in mice to human.ResultsWe found that modulating the gut microbiota with prebiotics modifies the actions of enteric neurons, thereby controlling duodenal contraction and subsequently attenuating hyperglycaemia in diabetic mice. We discovered that the signalling pathway involved in these effects depends on the synthesis of a bioactive lipid 12-hydroxyeicosatetraenoic acid (12-HETE) and the presence of mu-opioid receptors (MOR) on enteric neurons. Using pharmacological approaches, we demonstrated the key role of the MOR receptors and proliferator-activated receptor γ for the effects of 12-HETE. These findings are supported by human data showing a decreased expression of the proenkephalin and MOR messanger RNAs in the duodenum of patients with diabetic.ConclusionsUsing a prebiotic approach, we identified enkephalin and 12-HETE as new enterosynes with potential real beneficial and safety impact in diabetic human.
Published: 2020

16. Effects of Bisphenol S on hypothalamic neuropeptides regulating feeding behavior and apelin/APJ system in mice

Author: Anne Abot, Samir Aydi, Claude Knauf, Raja Rezg, and Bessem Mornagui
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Pro-Opiomelanocortin, Health, Toxicology and Mutagenesis, media_common.quotation_subject, Hypothalamus, Neuropeptide, Nerve Tissue Proteins, 010501 environmental sciences, Biology, Weight Gain, urologic and male genital diseases, 01 natural sciences, Eating, Mice, 03 medical and health sciences, Phenols, Internal medicine, Orexigenic, medicine, Animals, Obesity, RNA, Messenger, Sulfones, Benzhydryl Compounds, Receptor, 0105 earth and related environmental sciences, Apelin receptor, media_common, Apelin Receptors, Body Weight, Neuropeptides, Public Health, Environmental and Occupational Health, Appetite, Feeding Behavior, General Medicine, Pollution, Apelin, 030104 developmental biology, Endocrinology, Endocrine disruptor, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: Since 2010, Bisphenol A (BPA), an endocrine disruptor has been restricted and replaced by analogues like Bisphenol S (BPS). However, little is known about BPS effects and growing concern have suspected the “BPA-free” Label. Several recent studies suggest that BPS is associated with increased risk of diabetes and obesity. However, the underlying mechanisms remain unidentified. The current study investigates investigate BPS effects on hypothalamic neuropeptides regulating feeding behavior, either orexigenic or anorexigenic in Swiss Albino mice. We also studied the effect of BPS on the apelinergic system (apelin/apelin receptor (APJ)) as an original physiological system with pleiotropic actions. Bisphenol S at 25, 50, 100 µg/kg was administered to mice in water drink for 10 weeks started after weaning. Our results showed that BPS exposure alters orexigenic hypothalamic neuropeptide (AgRP) regulating feeding behavior but not anorexigenic neuropeptides (POMC, CART). Such orexigenic alterations may underlay appetite disorders leading to a concomitant food intake and body weight gain increase. In addition, data show that BPS affects the hypothalamic apelinergic system. We found a significant decrease in APJ mRNA but not in apelin expression. Based on hypothalamic APJ distribution, we suggested a potent specific physiological alteration of this receptor in mediating neuroendocrine responses in hypothalamus. Thus, our findings provide that BPS exposure could contribute to the development of obesity and metabolic disorders.
Published: 2018

17. Axe intestin-cerveau et contrôle du métabolisme glucidique

Author: Anne Abot, Lucie Murphy, and Claude Knauf
Subjects: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, Nutrition and Dietetics, business.industry, Medicine (miscellaneous), Medicine, business, Molecular biology, Intestinal absorption, 3. Good health
Abstract: Resume L’axe intestin-cerveau est un acteur majeur dans le maintien de l’homeostasie glucidique. Les informations nutritionnelles en provenance de l’intestin font intervenir des systemes de detection « classiques » appeles chemorecepteurs, mais egalement des mecanorecepteurs actives en reponse a des modifications de l’activite contractile de l’intestin. Ainsi, une grande partie des messages partant de l’intestin et se dirigeant vers l’hypothalamus ont une origine nerveuse et les modifications de l’activite des neurones hypothalamiques suite a cette information auront des repercussions sur le maintien de la glycemie. Dans un contexte pathologique, de nouveaux concepts ont ete decouverts et leur prise en compte pourrait ameliorer l’hyperglycemie et l’insulinoresistance du patient diabetique. Ainsi, il est possible de cibler les neurones du systeme nerveux enterique pour ralentir les contractions duodenales afin de diminuer l’hyperglycemie chronique, ceci en (1) diminuant l’absorption du glucose et (2) restaurant l’axe intestin-cerveau pour faciliter l’entree du glucose dans les tissus.
Published: 2018

18. Potentialities of Yeast Strains to be Used as Freeze-Drying Starters for the Production of Traditional Sorghum Beer in Côte d’Ivoire

Author: Koffi Maïzan Jean-Paul Bouatenin, Wahauwouélé Hermann Coulibaly, Djegba Marie Toka, Youan Bi, Alfred K. Kouamé, Fatoumata Camara, Anne Abot, and Kofﬁ Djè
Subjects: Freeze-drying, Horticulture, biology, Cote d ivoire, Food science, Sorghum, biology.organism_classification, Microbiology, Yeast
Published: 2017

19. Polyunsaturated fatty acid metabolites: biosynthesis in Leishmania and role in parasite/host interaction

Author: Julien Pujo, Jean Marie François, Jessica Dalloux-Chioccioli, Pauline Le Faouder, Anne Abot, Lucie Paloque, Teresa Pérez-Berezo, Marie-Ange Teste, Gilles Dietrich, Malwina Mainka, Alexis Valentin, Nicolas Cenac, Justine Bertrand-Michel, Sandra Bourgeade-Delmas, Nils Helge Schebb, Céline Deraison, Corinne Rolland, Catherine Blanpied, Laboratoire de chimie de coordination (LCC), 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-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-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 Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-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-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), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Faculty of Mathematics and Natural Sciences, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Institut National de la Recherche Agronomique (INRA)-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), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), MetaToul Lipidomics, 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)-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)-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)-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), 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), University of Wuppertal, Region Midi-Pyrenees, ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), European Project: 627487,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IOF,EPIMACASE(2014), 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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, 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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), 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)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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), Gulli, Marie-Hélène, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, THE ROLE OF ELASTASE/ELASTASE INHIBITOR IN DIALOG BETWEEN INTESTINAL EPITHELIAL CELLS AND MACROPHAGES IN INFLAMMATORY BOWEL DISEASES CONTEXT - EPIMACASE - - EC:FP7:PEOPLE2014-08-06 - 2016-08-05 - 627487 - VALID, Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-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)-MetaboHUB-MetaToul, 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)-Université Toulouse III - Paul Sabatier (UT3), 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)-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Cytochrome P450, 030204 cardiovascular system & hematology, Biochemistry, Mice, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Macrophage, Research Articles, Leishmania, chemistry.chemical_classification, biology, Chemistry, M2 Macrophage, 3. Good health, macrophages, Phenotype, Arachidonic acid, Docosahexaenoic acid, Fatty Acids, Unsaturated, ω-3, infection, Omega-3 fatty acids, Fatty acid metabolism, arachidonic acid, eicosanoids, omega-3, Infection, Polyunsaturated fatty acid, cytochrome P450, Macrophage polarization, CHO Cells, QD415-436, Biotechnologies, Host-Parasite Interactions, 03 medical and health sciences, Cricetulus, Animals, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Macrophages, Cell Biology, [CHIM.COOR] Chemical Sciences/Coordination chemistry, biology.organism_classification, Mice, Inbred C57BL, 030104 developmental biology, Metabolism, biology.protein, Eicosanoids, metabolism
Abstract: International audience; Inside the human host, Leishmania infection starts with phagocytosis of infective promastigotes by macrophages. In order to survive, Leishmania has developed several strategies to manipulate macrophage functions. Among these strategies, Leishmania as a source of bioactive lipids has been poorly explored. Herein, we assessed the biosynthesis of polyunsaturated fatty acid metabolites by infective and noninfective stages of Leishmania and further explored the role of these metabolites in macrophage polarization. The concentration of docosahexaenoic acid metabolites, precursors of proresolving lipid mediators, was increased in the infective stage of the parasite compared with the noninfective stage, and cytochrome P450-like proteins were shown to be implicated in the biosynthesis of these metabolites. The treatment of macrophages with lipids extracted from the infective forms of the parasite led to M2 macrophage polarization and blocked the differentiation into the M1 phenotype induced by IFN-γ. In conclusion, Leishmania polyunsaturated fatty acid metabolites, produced by cytochrome P450-like protein activity, are implicated in parasite/host interactions by promoting the polarization of macrophages into a proresolving M2 phenotype.
Published: 2019

20. Pharmacological inhibition of the F 1 -ATPase/P2Y 1 pathway suppresses the effect of apolipoprotein A1 on endothelial nitric oxide synthesis and vasorelaxation

Author: Paula Honorato, Marcelo González, Cendrine Cabou, Laure Frayssinhes, Bernard Masri, Claudio Aguayo, Valeria Aguilera, Laurent O. Martinez, Thibaut Duparc, Audren Fournel, Marcelo León, Anne Abot, Claude Knauf, Claudia Radojkovic, Guillaume Combes, Luis Briceño, Nicol Parada, Lamia Ghezali, 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), Département de physiologie humaine [UNIV Paul Sabatier, Toulouse] (Faculté de Pharmacie), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Department of Clinical Biochemistry and Immunology [Concepción, Chile] (Faculty of Pharmacy), Universidad de Concepción [Chile], Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-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), Group of Research and Innovation in Vascular Health [Chillan, Chile] (GRIVAS Health), Vascular Physiology Laboratory [Concepción, Chile] (Department of Physiology), Universidad de Concepción [Chile]-Faculty of Biological Sciences [Concepción, Chile], Department of Obstetrics and Gynecology [Concepción, Chile] (Faculty of Medicine), This work was supported by the 'Fondo Nacional de Desarrollo Científico y Tecnológico' (FONDECYT, #11121575, Chile), 'Dirección de Investigación Universidad de Concepción' (DIUC, #210.072.033-1.0, Chile), the French National Research Agency (ANR, #ANR-16-CE18-0014-01, HDLNEXT-THERAPEUTICS) and the 'Région Midi-Pyrénées - Occitanie' (CLE 2015, #14054132). 'INNOVA BIO BIO Chile para Apoyo de Tesis' fellowships were held by P. Honorato (#13.1285-EM.TES) and M. León (#12.127-EM.TES). L. Briceño was supported by 'Comisión Nacional de Investigación Científica y Tecnológica CONICYT-PCHA/Magíster Nacional' (#2014-63566), Chile., ANR-16-CE18-0014,HDL-NEXT-THERAPEUTICS,Nouvelles thérapies du HDL-cholestérol pour les maladies cardiovasculaire.(2016), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), MARTINEZ, Laurent, Nouvelles thérapies du HDL-cholestérol pour les maladies cardiovasculaire. - - HDL-NEXT-THERAPEUTICS2016 - ANR-16-CE18-0014 - AAPG2016 - VALID, Faculté des Sciences Pharmaceutiques, Universidad de Concepción - University of Concepcion [Chile], and Universidad de Concepción - University of Concepcion [Chile]-Faculty of Biological Sciences [Concepción, Chile]
Subjects: 0301 basic medicine, P2Y receptor, Physiology, ATPase, Vasodilation, 030204 cardiovascular system & hematology, Pharmacology, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, nitric oxide, purinergic receptors, Receptor, Physiologie, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, F1-ATPase, Chemistry, Purinergic receptor, Apolipoprotein A1, endothelial cells, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Adenosine diphosphate, 030104 developmental biology, biology.protein, lipids (amino acids, peptides, and proteins), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Autre (Sciences du Vivant), Lipoprotein
Abstract: C. Radojkovic and L.O. Martinez are co-senior authors.; International audience; AIM:The contribution of apolipoprotein A1 (APOA1), the major apolipoprotein of high-density lipoprotein (HDL), to endothelium-dependent vasodilatation is unclear, and there is little information regarding endothelial receptors involved in this effect. Ecto-F1 -ATPase is a receptor for APOA1, and its activity in endothelial cells is coupled to adenosine diphosphate (ADP)-sensitive P2Y receptors (P2Y ADP receptors). Ecto-F1 -ATPase is involved in APOA1-mediated cell proliferation and HDL transcytosis. Here we investigated the effect of lipid-free APOA1 and the involvement of ecto-F1 -ATPase and P2Y ADP receptors on nitric oxide (NO) synthesis and the regulation of vascular tone.METHOD:NO synthesis was assessed in human endothelial cells from umbilical veins (HUVECs) and isolated mouse aortas. Changes in vascular tone were evaluated by isometric force measurements in isolated human umbilical and placental veins and by assessing femoral artery blood flow in conscious mice.RESULTS:Physiological concentrations of lipid-free APOA1 enhanced endothelial NO synthesis, which was abolished by inhibitors of endothelial nitric oxide synthase (eNOS) and of the ecto-F1 -ATPase/P2Y1 axis. Accordingly, APOA1 inhibited vasoconstriction induced by thromboxane A2 receptor agonist and increased femoral artery blood flow in mice. These effects were blunted by inhibitors of eNOS, ecto-F1 -ATPase and P2Y1 receptor.CONCLUSIONS:Using a pharmacological approach, we thus found that APOA1 promotes endothelial NO production and thereby controls vascular tone in a process that requires activation of the ecto-F1 -ATPase/P2Y1 pathway by APOA1. Pharmacological targeting of this pathway with respect to vascular diseases should be explored. This article is protected by copyright. All rights reserved.
Published: 2019

21. Central Effects of Beta-Blockers May Be Due to Nitric Oxide and Hydrogen Peroxide Release Independently of Their Ability to Cross the Blood-Brain Barrier

Author: Alain Delarue, Claire Laurens, Anne Abot, and Claude Knauf
Subjects: infantile hemangioma, Propranolol, 030204 cardiovascular system & hematology, Pharmacology, Blood–brain barrier, Nitric oxide, lcsh:RC321-571, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, beta-blockers, 0302 clinical medicine, Nadolol, In vivo, medicine, propranolol, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, chemistry.chemical_classification, reactive oxygen species, Reactive oxygen species, General Neuroscience, Brief Research Report, blood-brain barrier, Atenolol, medicine.anatomical_structure, chemistry, Ex vivo, Neuroscience, medicine.drug
Abstract: Propranolol is the first-line treatment for infants suffering from infantile hemangioma. Recently, some authors raised the question of potential neurologic side effects of propranolol due to its lipophilic nature and thus its ability to passively cross the blood-brain barrier (BBB) and accumulate into the brain. Hydrophilic beta-blockers, such as atenolol and nadolol, where therefore introduced in clinical practice. In addition to their classical mode of action in the brain, circulating factors may modulate the release of reactive oxygen/nitrogen species (ROS/RNS) from endothelial cells that compose the BBB without entering the brain. Due to their high capacity to diffuse across membranes, ROS/RNS can reach neurons and modify their activity. The aim of this study was to investigate other mechanisms of actions in which these molecules may display a central effect without actually crossing the BBB. We first performed an oral treatment in mice to measure the accumulation of propranolol, atenolol and nadolol in different brain regions in vivo. We then evaluated the ability of these molecules to induce the release of nitric oxide (NO) and hydrogen peroxide (H2O2) ex vivo in the hypothalamus. As expected, propranolol is able to cross the BBB and is found in brain tissue in higher amounts than atenolol and nadolol. However, all of these beta-blockers are able to induce the secretion of signaling molecules (i.e., NO and/or H2O2) in the hypothalamus, independently of their ability to cross the BBB, deciphering a new potential deleterious impact of hydrophilic beta-blockers in the brain.
Published: 2019

22. Targeting the Enteric Nervous System to Treat Metabolic Disorders? 'Enterosynes' as Therapeutic Gut Factors

Author: Eve Wemelle, Anne Abot, Patrice D. Cani, Claude Knauf, and UCL - SSS/LDRI - Louvain Drug Research Institute
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Enteric Nervous System, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Insulin resistance, Diabetes mellitus, Internal medicine, Medicine, Glucose homeostasis, Animals, Humans, Obesity, Endocrine and Autonomic Systems, business.industry, Diabetes, medicine.disease, Phenotype, Diabetes Mellitus, Type 2, Hypothalamus, Enteric nervous system, business, Neuroscience, Hormone
Abstract: The gut-brain axis is of crucial importance for controlling glucose homeostasis. Alteration of this axis promotes the type 2 diabetes (T2D) phenotype (hyperglycaemia, insulin resistance). Recently, a new concept has emerged to demonstrate the crucial role of the enteric nervous system in the control of glycaemia via the hypothalamus. In diabetic patients and mice, modification of enteric neurons activity in the proximal part of the intestine generates a duodenal hyper-contractility that generates an aberrant message from the gut to the brain. In turn, the hypothalamus sends an aberrant efferent message that provokes a state of insulin resistance, which is characteristic of a T2D state. Targeting the enteric nervous system of the duodenum is now recognized as an innovative strategy for treatment of diabetes. By acting in the intestine, bioactive gut molecules that we called “enterosynes” can modulate the function of a specific type of neurons of the enteric nervous system to decrease the contraction of intestinal smooth muscle cells. Here, we focus on the origins of enterosynes (hormones, neurotransmitters, nutrients, microbiota, and immune factors), which could be considered therapeutic factors, and we describe their modes of action on enteric neurons. This unsuspected action of enterosynes is proposed for the treatment of T2D, but it could be applied for other therapeutic solutions that implicate communication between the gut and brain.
Published: 2019

23. Glucosensing in the gastrointestinal tract: Impact on glucose metabolism

Author: Anne Abot, Audren Fournel, Alysson Marlin, Claude Knauf, Patrice D. Cani, Carla Cirillo, and Charles Pasquio
Subjects: 0301 basic medicine, medicine.medical_specialty, Physiology, Hypothalamus, Reviews, 030209 endocrinology & metabolism, Type 2 diabetes, Biology, Carbohydrate metabolism, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, Diabetes mellitus, medicine, Animals, Homeostasis, Humans, Glucose homeostasis, Gastrointestinal tract, Hepatology, digestive, oral, and skin physiology, Gastroenterology, medicine.disease, Small intestine, Gastrointestinal Tract, Glucose, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Hyperglycemia
Abstract: The gastrointestinal tract is an important interface of exchange between ingested food and the body. Glucose is one of the major dietary sources of energy. All along the gastrointestinal tube, e.g., the oral cavity, small intestine, pancreas, and portal vein, specialized cells referred to as glucosensors detect variations in glucose levels. In response to this glucose detection, these cells send hormonal and neuronal messages to tissues involved in glucose metabolism to regulate glycemia. The gastrointestinal tract continuously communicates with the brain, especially with the hypothalamus, via the gut-brain axis. It is now well established that the cross talk between the gut and the brain is of crucial importance in the control of glucose homeostasis. In addition to receiving glucosensing information from the gut, the hypothalamus may also directly sense glucose. Indeed, the hypothalamus contains glucose-sensitive cells that regulate glucose homeostasis by sending signals to peripheral tissues via the autonomous nervous system. This review summarizes the mechanisms by which glucosensors along the gastrointestinal tract detect glucose, as well as the results of such detection in the whole body, including the hypothalamus. We also highlight how disturbances in the glucosensing process may lead to metabolic disorders such as type 2 diabetes. A better understanding of the pathways regulating glucose homeostasis will further facilitate the development of novel therapeutic strategies for the treatment of metabolic diseases.
Published: 2016

24. Rôle du fructo-oligosaccharide sur l’activité du système nerveux entérique : impact sur le métabolisme glucidique chez la souris diabétique

Author: Claire Laurens, Anne Abot, Claude Knauf, Patrice D. Cani, Cedric Moro, and Eve Wemelle
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract: Introduction et but de l’etude Le Systeme Nerveux Enterique (SNE) est un acteur primordial pour le controle de l’axe intestin-cerveau en conditions normale et pathologique (comme lors du Diabete de type 2 [DT2]). En effet, le DT2 se caracterise par une hypercontractilite duodenale (induite par des alterations du SNE) ce qui va induire des modifications hypothalamiques et contribuer a l’hyperglycemie retrouvee chez les patients diabetiques. Dans ce contexte, cibler le SNE afin de diminuer l’hypercontractilite et restaurer l’axe intestin-cerveau-peripherie constitue une nouvelle approche therapeutique pour traiter le DT2. Le prebiotique FOS (fructo-oligosaccharide) est connu pour moduler le microbiote intestinale de la souris diabetique, ameliorant la tolerance au glucose via, notamment, une diminution de l’inflammation du tissu adipeux. Cependant, l’impact de ce prebiotique sur l’activite du couple SNE/contraction duodenale reste inconnu. Nos objectifs sont donc, chez la souris sous regime gras ± FOS: – d’etudier l’activite contractile duodenale, – de determiner l’impact metabolique (tolerance au glucose, poids,…) de ces modifications d’activite contractile, – d’identifier les tissus impliques dans l’amelioration de la glycemie par la modulation du couple SNE/contraction par le FOS. Materiel et methodes Les souris (mâles, 9 sem) sont mises sous regime gras (HFD45 %) pendant 12 sem. Le prebiotique FOS (0,3 g/souris/jour) est donne dans l’eau de boisson des le debut du regime gras. Apres 12 sem, la contractilite duodenale a ete mesuree en condition ex vivo avec un capteur isotonique et l’expression des enzymes ChAT et nNOS (enzymes synthetisant des neurotransmetteurs impliques dans le controle des contractions) par RT-qPCR sur des fragments de duodenum. L’impact metabolique est mesure via des mesures regulieres de poids et un test de tolerance au glucose en fin de traitement. Enfin, les tissus impliques dans le metabolisme glucidique (foie, muscles, tissus adipeux…) ont ete preleve pour etudier les effets de la modulation de l’axe intestin-cerveau par le FOS sur les variations des taux d’ARNm de genes impliques dans le controle du metabolisme glucidique. Resultats et analyse statistique Le FOS entraine une diminution de la prise de poids des souris sous regime HFD45 % avec une amelioration de la tolerance au glucose sans modification de l’insulinemie. Ceci est associe a une diminution la frequence de contraction du duodenum correlee a une diminution de l’expression de l’enzyme ChAT (synthetisant de l’acetylcholine stimulant les contractions). La modification de la motilite duodenale induite par le FOS entraine une diminution de l’expression de genes impliques dans l’inflammation du tissu adipeux blanc. Conclusion Ainsi cibler le microbiote pour restaurer l’axe intestin-cerveau-peripherie, par une approche nutritionnelle permet de diminuer la contractilite duodenale de souris diabetiques en agissant sur le SNE, ce qui permet d’ameliorer le phenotype diabetique des souris sous regime HFD45 %. L’impact du microbiote sur le SNE et sur la regulation de l’axe intestin-cerveau-peripherie represente donc un nouveau mecanisme qui pourrait permettre le developpement de therapies innovantes pour traiter le DT2.
Published: 2020

25. Pharmacological inhibition of the F

Author: Cendrine, Cabou, Paula, Honorato, Luis, Briceño, Lamia, Ghezali, Thibaut, Duparc, Marcelo, León, Guillaume, Combes, Laure, Frayssinhes, Audren, Fournel, Anne, Abot, Bernard, Masri, Nicol, Parada, Valeria, Aguilera, Claudio, Aguayo, Claude, Knauf, Marcelo, González, Claudia, Radojkovic, and Laurent O, Martinez
Subjects: Male, Apolipoprotein A-I, Nitric Oxide Synthase Type III, Nitric Oxide, Adenosine Diphosphate, Mice, Inbred C57BL, Vasodilation, Mice, Proton-Translocating ATPases, Receptors, Purinergic P2Y1, Pregnancy, Human Umbilical Vein Endothelial Cells, Animals, Humans, Female, Endothelium, Signal Transduction
Abstract: The contribution of apolipoprotein A1 (APOA1), the major apolipoprotein of high-density lipoprotein (HDL), to endothelium-dependent vasodilatation is unclear, and there is little information regarding endothelial receptors involved in this effect. Ecto-FNitric oxide synthesis was assessed in human endothelial cells from umbilical veins (HUVECs) and isolated mouse aortas. Changes in vascular tone were evaluated by isometric force measurements in isolated human umbilical and placental veins and by assessing femoral artery blood flow in conscious mice.Physiological concentrations of lipid-free APOA1 enhanced endothelial NO synthesis, which was abolished by inhibitors of endothelial nitric oxide synthase (eNOS) and of the ecto-FUsing a pharmacological approach, we thus found that APOA1 promotes endothelial NO production and thereby controls vascular tone in a process that requires activation of the ecto-F
Published: 2018

26. Bisphenol S exposure affects gene expression related to intestinal glucose absorption and glucose metabolism in mice

Author: Anne Abot, Bessem Mornagui, Claude Knauf, and Raja Rezg
Subjects: Male, endocrine system, medicine.medical_specialty, Glycogenolysis, Health, Toxicology and Mutagenesis, Interleukin-1beta, 010501 environmental sciences, Carbohydrate metabolism, urologic and male genital diseases, 01 natural sciences, Mice, Sodium-Glucose Transporter 1, Phenols, Internal medicine, medicine, Environmental Chemistry, Animals, Sulfones, 0105 earth and related environmental sciences, Glucose Transporter Type 2, Apelin Receptors, biology, Chemistry, Tumor Necrosis Factor-alpha, Glucose transporter, Gluconeogenesis, General Medicine, Pollution, Apelin, Intestines, Endocrinology, Glucose, Gene Expression Regulation, Intestinal Absorption, Liver, biology.protein, Glucose-6-Phosphatase, GLUT2, Phosphoenolpyruvate carboxykinase, hormones, hormone substitutes, and hormone antagonists
Abstract: Bisphenol S, an industrial chemical, has raised concerns for both human and ecosystem health. Yet, health hazards posed by bisphenol S (BPS) exposure remain poorly studied. Compared to all tissues, the intestine and the liver are among the most affected by environmental endocrine disruptors. The aim of this study was to investigate the molecular effect of BPS on gene expression implicated in the control of glucose metabolism in the intestine (apelin and its receptor APJ, SGLT1, GLUT2) and in the liver (glycogenolysis and/or gluconeogenesis key enzymes (glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK)) and pro-inflammatory cytokine expression (TNF-α and IL-1β)). BPS at 25, 50, and 100 μg/kg was administered to mice in water drink for 10 weeks. In the duodenum, BPS exposure reduces significantly mRNA expression of sodium glucose transporter 1 (SGLT1), glucose transporter 2 (GLUT2), apelin, and APJ mRNA. In the liver, BPS exposure increases the expression of G6Pase and PEPCK, but does not affect pro-inflammatory markers. These data suggest that alteration of apelinergic system and glucose transporters expression could contribute to a disruption of intestinal glucose absorption, and that BPS stimulates glycogenolysis and/or gluconeogenesis in the liver. Collectively, we reveal that BPS heightens the risk of metabolic syndrome.
Published: 2018

27. Tamoxifen Elicits Atheroprotection through Estrogen Receptor α AF-1 But Does Not Accelerate Reendothelialization

Author: Alexia Vinel, Anne Abot, Audrey Billon-Galés, Gilles Flouriot, Jean-François Arnal, Pierre Gourdy, Etienne Grunenwald, Coralie Fontaine, Hortense Bergès, Marie-Cécile Valéra, 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), Transcription, environnement et cancer (Trec), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Selective Estrogen Receptor Modulators, Endothelium, Nuclear Receptor Coactivators, Estrogen receptor, 030204 cardiovascular system & hematology, Biology, Pharmacology, Pathology and Forensic Medicine, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, In vivo, medicine, Animals, Aorta, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Estrogen Receptor alpha, Ligand (biochemistry), medicine.disease, Plaque, Atherosclerotic, In vitro, 3. Good health, Mice, Inbred C57BL, Tamoxifen, Carotid Arteries, Atheroma, medicine.anatomical_structure, LDL receptor, Female, Endothelium, Vascular, Carotid Artery Injuries, Biomarkers, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: International audience; Based on both experimental and clinical data, tamoxifen has been proposed to have cardiovascular benefits, although the mechanism(s) contributing to that protective effect are still poorly understood. In vitro experiments demonstrated that tamoxifen elicits its transcriptional effect through estrogen receptor (ER) α, but other targets can participate in its actions. However, although tamoxifen selectively activates the activating function (AF)-1 of ERα, we recently showed that this ERα subfunction is dispensable for the atheroprotective action of 17β-estradiol (E2), the main ligand of ERs. The goal of the present work is to determine to which extent ERα and its AF-1 mediate the vasculoprotective action of tamoxifen. Our data confirm that tamoxifen exerts an atheroprotective action on low density lipoprotein receptor (LDL-r(-/-)) female mice, but, in contrast to E2, it fails to accelerate reendothelialization after carotid electric injury. Tamoxifen and E2 elicit differences in gene expression profiles in the mouse aorta. Finally, the atheroprotective action of tamoxifen is abrogated in ERα(-/-)LDL-r(-/-) mice and in LDL-r(-/-) mice selectively deficient in ERαAF-1 (ERαAF-1(0/0)LDL-r(-/-)). Our results demonstrate, for the first time to our knowledge, that tamoxifen mediates its actions in vivo through the selective activation of ERαAF-1, which is sufficient to prevent atheroma, but not to accelerate endothelial healing.
Published: 2013

28. CAZyChip: dynamic assessment of exploration of glycoside hydrolases in microbial ecosystems

Author: Michael J. O’Donohue, Lucas Auer, Elisabeth Laville, Bernard Henrissat, Claire Dumon, Vincent Lombard, Guillermina Hernandez-Raquet, Véronique Anton Leberre, Sophie Lamarre, Anne Abot, Adèle Lazuka, Grégory Arnal, Delphine Labourdette, Gabrielle Potocki-Véronèse, Lidwine Trouilh, Architecture et fonction des macromolécules biologiques ( AFMB ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA ), Conseil Régional Midi-Pyrénées 12053333, IDEX Univ. Toulouse 2014–628, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Architecture et fonction des macromolécules biologiques (AFMB), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), King Abdulaziz University, Leberre, Véronique, Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and 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)
Subjects: 0301 basic medicine, Glycan, CAZy, Glycoside Hydrolases, [SDV]Life Sciences [q-bio], Computational biology, Microarray, Microbial functional diversity, Proteomics, medicine.disease_cause, Transcriptomic analysis, 03 medical and health sciences, Bacterial Proteins, Cell Wall, Polysaccharides, Databases, Genetic, medicine, Genetics, Escherichia coli, Glycoside hydrolase, Bioprocess, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], ComputingMilieux_MISCELLANEOUS, Oligonucleotide Array Sequence Analysis, biology, business.industry, Sequence Analysis, RNA, Gene Expression Regulation, Bacterial, Plants, CAZymes detection, Biotechnology, Plant cell wall degradation, 030104 developmental biology, Metagenomics, biology.protein, Metagenome, DNA microarray, business, hormones, hormone substitutes, and hormone antagonists, Research Article, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: Background Microorganisms constitute a reservoir of enzymes involved in environmental carbon cycling and degradation of plant polysaccharides through their production of a vast variety of Glycoside Hydrolases (GH). The CAZyChip was developed to allow a rapid characterization at transcriptomic level of these GHs and to identify enzymes acting on hydrolysis of polysaccharides or glycans. Results This DNA biochip contains the signature of 55,220 bacterial GHs available in the CAZy database. Probes were designed using two softwares, and microarrays were directly synthesized using the in situ ink-jet technology. CAZyChip specificity and reproducibility was validated by hybridization of known GHs RNA extracted from recombinant E. coli strains, which were previously identified by a functional metagenomic approach. The GHs arsenal was also studied in bioprocess conditions using rumen derived microbiota. Conclusions The CAZyChip appears to be a user friendly tool for profiling the expression of a large variety of GHs. It can be used to study temporal variations of functional diversity, thereby facilitating the identification of new efficient candidates for enzymatic conversions from various ecosystems. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2988-4) contains supplementary material, which is available to authorized users.
Published: 2016

29. Central chronic apelin infusion decreases energy expenditure and thermogenesis in mice

Author: Anne Abot, Philippe Valet, Alexandre Lucas, Claude Knauf, Anne Drougard, Tereza Bautzova, Xavier Fioramonti, Audren Fournel, Alysson Marlin, Thibaut Duparc, Cedric Moro, Sophie Le-Gonidec, Patrice D. Cani, Etienne Meunier, Aurélie Batut, Jean Lesage, Katie Louche, 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 ), Max Planck Institute of Immunobiology and Epigenetics, Institut de Recherche en Santé Digestive - IRSD [Purpan, Toulouse], Institut National de la Recherche Agronomique ( INRA ) -Université Paul Sabatier - Toulouse 3 ( UPS ) -Ecole Nationale Vétérinaire de Toulouse-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Purpan - Centre Hospitalier Universitaire (CHU) de Toulouse, Focal Area Infection Biology, Biozentrum, University of Basel ( Unibas ), Environnement périnatal et croissance, 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 ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Walloon Excellence in Life sciences and BIOtechnology ( WELBIO ), Université Catholique de Louvain ( UCL ), Microbiota, Université Catholique de Louvain ( UCL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Société Francaise de Nutrition (SFN), the Fondation Recherche Médicale (FRM) (Grant ING20150532586)the Societe Francophone du Diabète (Allocations Exceptionnelles 2016), ANR-12-JSV1-0010,DYNAMISE,Impact de la dynamique des gouttelettes lipidiques dans le muscle squelettique sur le métabolisme oxydatif et la sensibilité à l’insuline ( 2012 ), 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, Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-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), University of Basel (Unibas), Environnement périnatal et croissance - EA 4489 (EPS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Walloon Excellence in Life sciences and BIOtechnology [Liège] (WELBIO), Université Catholique de Louvain = Catholic University of Louvain (UCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-12-JSV1-0010,DYNAMISE,Impact de la dynamique des gouttelettes lipidiques dans le muscle squelettique sur le métabolisme oxydatif et la sensibilité à l'insuline(2012), UCL - SSS/LDRI - Louvain Drug Research Institute, université de Bourgogne, CSGA, Jeunes Chercheuses et Jeunes Chercheurs - Impact de la dynamique des gouttelettes lipidiques dans le muscle squelettique sur le métabolisme oxydatif et la sensibilité à l'insuline - - DYNAMISE2012 - ANR-12-JSV1-0010 - JC - VALID, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), 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 Catholique de Louvain (UCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-12-JSV1-0010,DYNAMISE,Impact de la dynamique des gouttelettes lipidiques dans le muscle squelettique sur le métabolisme oxydatif et la sensibilité à l’insuline(2012), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Cani, Patrice D., and Knauf, Claude
Subjects: 0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Interleukin-1beta, Gene Expression, Nitric Oxide Synthase Type II, Adipose tissue, adipose-tissue, Mice, 0302 clinical medicine, Adipose Tissue, Brown, Brown adipose tissue, circadian clock, Glucose homeostasis, Uncoupling Protein 1, PRDM16, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Multidisciplinary, brown fat, Thermogenesis, Type 2 diabetes, food-intake, [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, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Thermogenin, 3. Good health, Apelin, DNA-Binding Proteins, Infusions, Intraventricular, medicine.anatomical_structure, Hypothalamus, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Alimentation et Nutrition, medicine.medical_specialty, Biology, diabetic mice, signaling controls, Article, 03 medical and health sciences, Internal medicine, medicine, Animals, Food and Nutrition, gut microbiota, insulin-resistant mice, Neurosciences, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, ddc:616.8, metabolic-disorders, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Neurons and Cognition, glucose-homeostasis, Energy Metabolism, 030217 neurology & neurosurgery, Transcription Factors
Abstract: Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions. We have shown that chronic icv infusion of apelin increases the expression of pro-inflammatory factors in the hypothalamus associated with an increase in plasma interleukin-1 beta. In parallel, mice infused with icv apelin exhibit a significant lower energy expenditure coupled to a decrease in PGC1alpha, PRDM16 and UCP1 expression in brown adipose tissue which could explain the alteration of thermogenesis in these mice. These data provide compelling evidence that central apelin contributes to the development of type 2 diabetes by altering energy expenditure, thermogenesis and fat browning.
Published: 2016

30. CAZyChip: a bioChip for bacterial glycoside hydrolases detection and dynamic exploration of microbial diversity for plant cell wall hydrolysis

Author: Anne Abot, Delphine Labourdette, Lidwine Trouilh, Sophie Lamarre, Gabrielle Potocki Veronese, Lucas Auer, Adèle Lazuka, Guillermina Hernandez-Raquet, Bernard Henrissat, Donohue, Michael O., Claire Dumon, veronique LE BERRE-ANTON, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), 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), Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA)
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2015

31. Phytochip: Development of a DNA-microarray for rapid and accurate identification of Pseudo-nitzschia spp and other harmful algal species

Author: Charlotte Noyer, Lidwine Trouilh, Véronique Anton Leberre, Catherine Dreanno, Anne Abot, Institut Français de Recherche pour l'Exploitation de la Mer - Brest (IFREMER), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), 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), ANR-10-STRA-0010,COMANCHE,Interactions écosystémiques et impacts anthropiques dans les populations de Coquilles St-Jacques de la Manche(2010), Institut Français de Recherche pour l'Exploitation de la Mer - Brest (IFREMER Centre de Bretagne), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, Microbiology (medical), Time Factors, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Ribosomal oligonucleotide probes, Context (language use), Computational biology, Biology, Microarray, 01 natural sciences, Microbiology, 03 medical and health sciences, Multiplex, Molecular Biology, 030304 developmental biology, Oligonucleotide Array Sequence Analysis, Diatoms, 0303 health sciences, HAB, 010604 marine biology & hydrobiology, Environmental monitoring, Sequence Analysis, DNA, biology.organism_classification, DNA extraction, Monitoring program, Molecular biology, Karenia, Dinoflagellida, Pseudo-nitzschia, RRNA Operon, DNA microarray
Abstract: International audience; Detection of harmful algal blooms has become a challenging concern because of the direct impacts on public health and economy. The identification of toxic dinoflagellates and diatoms in monitoring programs requires an extensive taxonomic expertise and is time consuming. Advances in molecular biology have allowed the development of new approaches, more rapid, accurate and cost-effective for detecting these microorganisms. In this context, we developed a new DNA microarray (called, Phytochip) for the simultaneous detection of multiple HAB species with a particular emphasis on Pseudo-nitzschia species. Oligonucleotide probes were designed along the rRNA operon. After DNA extraction, the target rDNA genes were amplified and labeled using an asymmetric PCR; then, the amplicons were hybridized to the oligonucleotide probes present on the chips. The total assay from seawater sampling to data acquisition can be performed within a working day. Spec-ificity and sensitivity were assessed by using monoclonal cultures, mixtures of species and field samples spiked with a known amount of cultured cells. The Phytochip with its 81 validated oligonucleotide probes was able to detect 12 species of Pseudo-nitzschia and 11 species of dinoflagellates among which were 3 species of Karenia and 3 species of Alexandrium. The Phytochip was applied to environmental samples already characterized by light microscopy and cloned into DNA libraries. The hybridizations on the Phytochip were in good agreement with the sequences retrieved from the clone libraries and the microscopic observations. The Phytochip enables a reliable multiplex detection of phytoplankton and can assist a water quality monitoring program as well as more general ecological research.
Published: 2015

32. The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation

Author: Claude Knauf, Françoise Lenfant, Marine Adlanmerini, Muriel Laine, Shyamala S. Rajan, Isabelle Raymond-Letron, Anne Drougard, Isabelle Muller, Daniel Henrion, Philippe Valet, Christel Pequeux, Anne Abot, Romain Solinhac, Jean-François Arnal, Marie Cécile Valera, Aurelie Fabre, John A. Katzenellenbogen, Alain Milon, Mélanie Mestdagt, Gilles Flouriot, François Ferrière, Coralie Fontaine, Jean-Michel Foidart, Geoffrey L. Greene, Céline Gérard, Anne Gompel, Pierre Gourdy, Benita S. Katzenellenbogen, Melissa Buscato, 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), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre national de référence des angioedemes, Laboratory of Tumor and Developmental Biology, Université de Liège-CHU Sart-Tilman, Department of Molecular and Integrative Physiology, University of Illinois System, Institut de médecine moléculaire de Rangueil (I2MR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie des Tumeurs et du Développement), Université de Liège, The work at the INSERM unit U1048 was supported by INSERM, Université de Toulouse III and Faculté de Médecine Toulouse-Rangueil, Fondation de France, Conseil Régional Midi-Pyrénées and Fondation pour la Recherche Médicale (FRM). A. Abot was supported by a grant from the Groupe de Réflexion sur la Recherche Cardiovasculaire. The NMR facility is part of the genotoul-Ibisa PICT platform and was funded by CNRS, région Midi-Pyrénées, and European structural funds. The work at INSERM U1083-CNRS-UMR 6214 is supported by INSERM, CNRS, CHU and Université d'Angers, Fondation de France, Fondation de l'Avenir, and Conseil Régional Pays de la Loire. The work at ULg, GIGA-cancer was supported by grants from the F.R.S.-FNRS (Belgium), the DGO6 from SPW (Belgium), the IUAP (Belspo, Belgium). This work was supported by National Institutes of Health Grants PHS5R01 DK015556 to J.A.K., Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Models, Molecular, [SDV]Life Sciences [q-bio], Gene Expression, Estrogen receptor, Protein Structure, Secondary, chemistry.chemical_compound, 0302 clinical medicine, Research Articles, Mice, Knockout, 0303 health sciences, Molecular Structure, Reverse Transcriptase Polymerase Chain Reaction, Estetrol, Hep G2 Cells, Immunohistochemistry, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MCF-7 Cells, Molecular Medicine, Female, estrogen receptor, medicine.medical_specialty, endothelium, Endothelium, medicine.drug_class, Ovariectomy, Blotting, Western, Biology, 03 medical and health sciences, Internal medicine, Coactivator, medicine, Animals, Humans, Estrogen receptor beta, Cell Proliferation, 030304 developmental biology, Cell Nucleus, uterus, Cell Membrane, Estrogen Receptor alpha, Protein Structure, Tertiary, Mice, Inbred C57BL, Endocrinology, chemistry, Estrogen, Nuclear receptor coactivator 3, Endothelium, Vascular, Estrogen receptor alpha, HeLa Cells
Abstract: International audience; Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand-binding domain bound to 17β-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.
Published: 2014

33. Mutation of the palmitoylation site of estrogen receptor α in vivo reveals tissue-specific roles for membrane versus nuclear actions

Author: Andrée Krust, Coralie Fontaine, Romain Solinhac, Aurelie Fabre, Pierre Chambon, Lucile Sautier, Sung Hoon Kim, Françoise Lenfant, Daniel Henrion, Emilie Vessieres, Marine Adlanmerini, Pierre Gourdy, Jean-François Arnal, John A. Katzenellenbogen, Anne-Laure Guihot, Philippe Liere, Frédéric Boudou, Philip W. Shaul, Isabelle Raymond-Letron, Anne Abot, 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), ANEXPLO, Institut de pharmacologie et de biologie structurale (IPBS), 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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System-University of Illinois System, Stéroides et système nerveux : physiopathologie moléculaire et clinique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Department of Pediatrics, University of Texas Southwestern Medical Center [Dallas], The work at I2MC-INSERM U1048 is supported by Institut National de la Santé et de la Recherche Médicale, Université et CHU de Toulouse, Faculté de Médecine Toulouse-Rangueil, Fondation pour la Recherche Médicale, Fondation de France, Fondation de l'Avenir, Conseil Régional Midi-Pyrénées, and AVIESAN-Astra-Zeneca. The work at INSERM U1083-Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche 6214 is supported by INSERM, CNRS, Centre Hospitalier Universitaire and Université d'Angers, Fondation de France, Fondation de l'Avenir and Conseil Régional Pays de la Loire, Conseil Régional Midi-Pyrénées, and Fondation pour la Recherche Médicale. M.A. and A.A. were supported by grants from the Ministère de la Recherche and Groupe de Réflexion sur la Recherche Cardiovasculaire, respectively. This work was supported by National Institutes of Health Grants DK015556 and HL087564 (to J.A.K. and P.W.S., respectively)., 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, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), 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 Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Estrogen receptor, Mice, Transactivation, Cell Movement, Image Processing, Computer-Assisted, MESH: Animals, MESH: Endothelial Cells, Receptor, MESH: Cell Movement, MESH: Estrogen Receptor alpha, fertility, Regulation of gene expression, Multidisciplinary, Immunohistochemistry, MESH: Image Processing, Computer-Assisted, Cell biology, PNAS Plus, MESH: Uterus, Female, vascular effects nongenomic effects, MESH: Computational Biology, MESH: Ovary, MESH: Cell Nucleus, medicine.medical_specialty, MESH: Mice, Transgenic, Steroid hormone receptor, Lipoylation, Blotting, Western, MESH: Receptor Cross-Talk, MESH: Lipoylation, Mice, Transgenic, Biology, genomic actions, In vivo, MESH: Analysis of Variance, Internal medicine, medicine, Animals, Point Mutation, MESH: Blotting, Western, MESH: Mice, MESH: Point Mutation, Cell Nucleus, Analysis of Variance, Cell Membrane, Ovary, Uterus, Estrogen Receptor alpha, Wild type, Computational Biology, Endothelial Cells, MESH: Immunohistochemistry, Receptor Cross-Talk, Microarray Analysis, MESH: Microarray Analysis, Endocrinology, MESH: Female, Estrogen receptor alpha, MESH: Cell Membrane
Abstract: International audience; Estrogen receptor alpha (ERα) activation functions AF-1 and AF-2 classically mediate gene transcription in response to estradiol (E2). A fraction of ERα is targeted to plasma membrane and elicits membrane-initiated steroid signaling (MISS), but the physiological roles of MISS in vivo are poorly understood. We therefore generated a mouse with a point mutation of the palmitoylation site of ERα (C451A-ERα) to obtain membrane-specific loss of function of ERα. The abrogation of membrane localization of ERα in vivo was confirmed in primary hepatocytes, and it resulted in female infertility with abnormal ovaries lacking corpora lutea and increase in luteinizing hormone levels. In contrast, E2 action in the uterus was preserved in C451A-ERα mice and endometrial epithelial proliferation was similar to wild type. However, E2 vascular actions such as rapid dilatation, acceleration of endothelial repair, and endothelial NO synthase phosphorylation were abrogated in C451A-ERα mice. A complementary mutant mouse lacking the transactivation function AF-2 of ERα (ERα-AF2(0)) provided selective loss of function of nuclear ERα actions. In ERα-AF2(0), the acceleration of endothelial repair in response to estrogen-dendrimer conjugate, which is a membrane-selective ER ligand, was unaltered, demonstrating integrity of MISS actions. In genome-wide analysis of uterine gene expression, the vast majority of E2-dependent gene regulation was abrogated in ERα-AF2(0), whereas in C451A-ERα it was nearly fully preserved, indicating that membrane-to-nuclear receptor cross-talk in vivo is modest in the uterus. Thus, this work genetically segregated membrane versus nuclear actions of a steroid hormone receptor and demonstrated their in vivo tissue-specific roles.
Published: 2013

34. Lessons from the dissection of the activation functions (AF-1 and AF-2) of the estrogen receptor alpha in vivo

Author: Anne Abot, Marie-Cécile Valéra, Françoise Lenfant, Henrik Laurell, Pierre Gourdy, Coralie Fontaine, and Jean-François Arnal
Subjects: medicine.medical_specialty, medicine.drug_class, Clinical Biochemistry, Central nervous system, Estrogen receptor, Biology, Biochemistry, Mice, Endocrinology, Breast cancer, Receptors, Glucocorticoid, Internal medicine, medicine, Animals, Humans, Receptor, Molecular Biology, Estrogen receptor beta, Pharmacology, Organic Chemistry, Estrogen Receptor alpha, medicine.disease, Menopause, medicine.anatomical_structure, Estrogen, Cancer research, Estrogen receptor alpha
Abstract: Estrogens influence most of the physiological processes in mammals, including but not limited to reproduction, cognition, behavior, vascular system, metabolism and bone integrity. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen influence the pathophysiology of numerous diseases, including cancer (of the reproductive tract as breast, endometrial but also colorectal, prostate,…), as well as neurodegenerative, inflammatory-immune, cardiovascular and metabolic diseases, and osteoporosis. These actions are mediated by the activation of estrogen receptors (ER) alpha (ERα) and beta (ERβ), which regulate target gene transcription (genomic action) through two independent activation functions (AF)-1 and AF-2, but can also elicit rapid membrane initiated steroid signals (MISS). Targeted ER gene inactivation has shown that although ERβ plays an important role in the central nervous system and in the heart, ERα appears to play a prominent role in most of the other tissues. Pharmacological activation or inhibition of ERα and/or ERβ provides already the basis for many therapeutic interventions, from hormone replacement at menopause to prevention of the recurrence of breast cancer. However, the use of these estrogens or selective estrogen receptors modulators (SERMs) have also induced undesired effects. Thus, an important challenge consists now to uncouple the beneficial actions from other deleterious ones. The in vivo molecular "dissection" of ERα represents both a molecular and integrated approach that already allowed to delineate in mouse the role of the main "subfunctions" of the receptor and that could pave the way to an optimization of the ER modulation.
Published: 2012

35. Correction of RT-qPCR data for genomic DNA-derived signals with ValidPrime

Author: Anne Abot, Jean-François Arnal, Mikael Kubista, Jason S. Iacovoni, Henrik Laurell, Jean-José Maoret, David Svec, Simon, Marie Francoise, 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), Laboratory of Gene Expression, Czech Academy of Sciences [Prague] (CAS), TATAA Biocenter AB, Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), 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), Faculté de Médecine [Rangueil], 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. Funding for the open access charge: Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France., Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), 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), Faculté de Médecine, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]
Subjects: MESH: DNA Primers, MESH: DNA Contamination, Biology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, law, MESH: Mice, Inbred C57BL, MESH: Reverse Transcriptase Polymerase Chain Reaction, Genetics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, Polymerase chain reaction, 030304 developmental biology, DNA Primers, 0303 health sciences, Reverse Transcriptase Polymerase Chain Reaction, MESH: Genomics, MESH: DNA, DNA, Genomics, DNA Contamination, Molecular biology, Reverse transcriptase, Mice, Inbred C57BL, genomic DNA, Real-time polymerase chain reaction, Reference sample, chemistry, 13. Climate action, 030220 oncology & carcinogenesis, Methods Online, RNA extraction
Abstract: International audience; Genomic DNA (gDNA) contamination is an inherent problem during RNA purification that can lead to non-specific amplification and aberrant results in reverse transcription quantitative PCR (RT-qPCR). Currently, there is no alternative to RT(-) controls to evaluate the impact of the gDNA background on RT-PCR data. We propose a novel method (ValidPrime) that is more accurate than traditional RT(-) controls to test qPCR assays with respect to their sensitivity toward gDNA. ValidPrime measures the gDNA contribution using an optimized gDNA-specific ValidPrime assay (VPA) and gDNA reference sample(s). The VPA, targeting a non-transcribed locus, is used to measure the gDNA contents in RT(+) samples and the gDNA reference is used to normalize for GOI-specific differences in gDNA sensitivity. We demonstrate that the RNA-derived component of the signal can be accurately estimated and deduced from the total signal. ValidPrime corrects with high precision for both exogenous (spiked) and endogenous gDNA, contributing ∼60% of the total signal, whereas substantially reducing the number of required qPCR control reactions. In conclusion, ValidPrime offers a cost-efficient alternative to RT(-) controls and accurately corrects for signals derived from gDNA in RT-qPCR.
Published: 2012

36. Activation function 2 (AF2) of estrogen receptor-{alpha} is required for the atheroprotective action of estradiol but not to accelerate endothelial healing

Author: Andrée Krust, Pierre Chambon, Gilles Flouriot, Pierre Gourdy, Jean-François Arnal, Alain-Pierre Gadeau, Audrey Billon-Galés, Hortense Berges, Coralie Fontaine, Françoise Lenfant, Céline E. Toutain, Anne Abot, 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), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Adaptation cardiovasculaire à l'ischemie, Université Bordeaux Segalen - Bordeaux 2-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 de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), and Simon, Marie Francoise
Subjects: Transcriptional Activation, medicine.medical_specialty, Endothelium, medicine.drug_class, [SDV]Life Sciences [q-bio], Estrogen receptor, 030204 cardiovascular system & hematology, Biology, Protective Agents, Mice, 03 medical and health sciences, 0302 clinical medicine, In vivo, Internal medicine, medicine, Animals, Humans, Aorta, 030304 developmental biology, Mice, Knockout, Regulation of gene expression, Wound Healing, 0303 health sciences, Multidisciplinary, Estradiol, Kinase, Body Weight, Uterus, Estrogen Receptor alpha, Reproducibility of Results, Hep G2 Cells, Organ Size, Biological Sciences, Atherosclerosis, Cell biology, [SDV] Life Sciences [q-bio], Endocrinology, medicine.anatomical_structure, Gene Expression Regulation, Cell culture, Estrogen, Female, Endothelium, Vascular, Estrogen receptor alpha, HeLa Cells
Abstract: 17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF2 0 ) . Our results prove four points. ( i ) Compared with WT ERα, the ability of ERαAF2 0 to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. ( ii ) The uterotrophic action of E2 was totally absent in ERαAF2 0 mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. ( iii ) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of ERαAF2 0 in vivo. ( iv ) Finally, the atheroprotective effect of E2 was abrogated in ERαAF2 0 LDL-r −/− mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect.
Published: 2011

37. 0053: The estrogen receptor alpha C451 palmitoylation site is absolutely required for vascular membrane-initiated action of estrogens in mice

Author: Anne Abot, Coralie Fontaine, Aurelie Fabre, Andrée Krust, Pierre Gourdy, Emilie Vessieres, Lucile Sautier, Sung Hoon Kim, Françoise Lenfant, Daniel Henrion, Jean-François Arnal, Phillippe Lière, John A. Katzenellenbogen, Anne-Laure Guihot, Marine Adlanmerini, Romain Solinhac, Isabelle Raymond-Letron, Frédéric Boudou, Philippe W. Shaul, and Pierre Chambon
Subjects: Regulation of gene expression, medicine.medical_specialty, business.industry, Steroid hormone receptor, Mutant, Cell biology, Transactivation, Endocrinology, In vivo, Internal medicine, Gene expression, Medicine, Phosphorylation, business, Cardiology and Cardiovascular Medicine, Estrogen receptor alpha
Abstract: Estrogen Receptor alpha (ERα) activation functions AF-1 and AF-2 classically mediate gene transcription in response to estradiol (E2). A fraction of ERα is targeted to plasma membrane and elicits membrane-initiated steroid signalling (MISS), but the physiological roles of MISS in vivo are poorly understood. We therefore generated a mouse with a point mutation of the palmitoylation site of ERα (C451A-ERα) to obtain membrane-specific loss-of-function of ERα. The abrogation of membrane localization of ERα in vivo was confirmed in primary hepatocytes, and it resulted in female infertility with abnormal ovaries lacking corpora lutea and increase in luteinizing hormone levels. In contrast, E2 action in the uterus was preserved in C451A-ERα mice and endometrial epithelial proliferation was similar to wild-type. However, E2 vascular actions such as rapid dilatation, the acceleration of endothelial repair and endothelial NO synthase phosphorylation were abrogated in C451A-ERα mice. A complementary mutant mouse lacking the transactivation function AF-2 of ER (ERα-AF2°) provided selective loss-of-function of nuclear ERα actions. In ERα-AF2°, the acceleration of endothelial repair in response to estrogen-dendrimer conjugate, which is a membrane-selective ER ligand, was unaltered, demonstrating integrity of MISS actions. In genome-wide analysis of uterine gene expression, the vast majority of E2-dependent gene regulation was abrogated in ERα-AF2° whereas in C451A-ERα it was nearly fully preserved, indicating that membrane-to-nuclear receptor crosstalk in vivo is modest in the uterus. Thus, this work is the first to genetically segregate membrane versus nuclear actions of a steroid hormone receptor and to demonstrate their in vivo tissue-specific roles.
Published: 2014
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38. 199 ARTICULAR LEVELS OF ADIPONECTIN ARE NOT CHONDROPROTECTIVE IN 3D CULTURES OF HUMAN CHONDROCYTES

Author: Anne Abot, J.-Y. Jouzeau, V. Olive, S. Sebillaud, P. Netter, David Moulin, and Arnaud Bianchi
Subjects: medicine.medical_specialty, Endocrinology, Adiponectin, Rheumatology, business.industry, Internal medicine, medicine, Biomedical Engineering, Orthopedics and Sports Medicine, business
Published: 2007
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39. Respective roles of activation function -1 and -2 of estrogen receptor alpha in the uterine proliferative actions of estradiol in mouse

Author: I. Raymond, Coralie Fontaine, Henrik Laurell, J.-F. Arnal, H. Bergès, and Anne Abot
Subjects: medicine.medical_specialty, Endocrinology, Chemistry, Endocrinology, Diabetes and Metabolism, Internal medicine, Activation function, medicine, General Medicine, Estrogen receptor alpha, Estrogen receptor beta
Published: 2012

40. Mutation of palmitoylation site of Estrogen Receptor ER alpha in vivo reveals tissue-specific roles for membrane versus genomic effects of estrogens

Author: Jean-François Arnal, John A. Katzenellenbogen, Anne Abot, Philip W. Shaul, Isabelle Raymond-Letron, Pierre Chambon, Romain Solinhac, Coralie Fontaine, Françoise Lenfant, Frédéric Boudou, Philippe Liere, Aurelie Fabre, Sung Hoon Kim, Pierre Gourdy, Andrée Krust, Daniel Henrion, and Marine Adlanmerini
Subjects: Regulation of gene expression, medicine.medical_specialty, Activator (genetics), Endocrinology, Diabetes and Metabolism, Mutant, Estrogen receptor, General Medicine, Biology, Cell biology, Endocrinology, medicine.anatomical_structure, In vivo, Internal medicine, Gene expression, medicine, Estrogen receptor alpha, Corpus luteum
Abstract: Introduction Estradiol (E2) binds to Estrogen Receptor alpha (ERα) activation functions (AF-1 and -2) and regulates gene transcription. A fraction of ERa is targeted to plasma membrane and elicits membrane-initiated steroid signalling (MISS) but its physiological role has never been directly investigated in vivo. Methods We thus generated a mouse mutated for the palmitoylation site (C451A-ERα) by homologous recombination, leading to an abrogation of membrane localization of ERα. Results Surprisingly, this single mutation leads to total female infertility with abnormal ovaries lacking corpus luteum and hence low progesterone production. However, E2 proliferative action was completely preserved in the uterus of C451A-ERa mutant mice and endometrial epithelial proliferation was similar to wild-type. On the opposite, E2 vascular effects, such as rapid dilatation, acceleration of endothelial healing and endothelial NO synthase phosphorylation were abrogated in arteries of C451A-ERa mice. In striking contrast, in mice inactivated for genomic effects (ERa-AF2°), acceleration of re-endothelialization using membrane-selective activator estrogen-dendrimer conjugate (EDC) was preserved, demonstrating the integrity of the MISS actions in ERa-AF2°. Using a large scale analysis of uterine gene expression, almost all uterine E2-dependent gene expression was abrogated in ERa-AF2°, whereas in C451A mice, gene regulation was essentially similar to wild-type, revealing that this uterine transcriptional response depends primarily on genomic/nuclear functions of ERα. Conclusion These models provide evidence for the first time of the physiological role of MISS effects of ERα in vivo and delineate tissue specific roles of membrane and nuclear actions of ERα.
Published: 2014

41. Influence de l’adiponectine sur les fonctions chondrocytaires dans l’arthrose

Author: Anne Abot, Nathalie Presle, Pascale Gegout-Pottie, Didier Mainard, Jean-Yves Jouzeau, David Moulin, Pierre-Jean Francin, Jean-Baptiste Gross, and Arnaud Bianchi
Subjects: Orthopedics and Sports Medicine, Surgery
Published: 2013

42. 246 Respective roles of transactivating function-1 and -2 of estrogen receptor alpha in the vasculoprotective actions of estradiol

Author: Coralie Fontaine, Anne Abot, Françoise Lenfant, Pierre Gourdy, Jean-François Arnal, Audrey Billon, and Henrik Laurell
Subjects: chemistry.chemical_classification, Gene isoform, medicine.medical_specialty, business.industry, Amino acid, Endocrinology, chemistry, Selective estrogen receptor modulator, Transcription (biology), Internal medicine, LDL receptor, medicine, Ovariectomized rat, Cardiology and Cardiovascular Medicine, business, Estrogen receptor alpha, Estrogen receptor beta
Abstract: Full length 66 kDa estrogen receptor alpha (ER) stimulates target gene transcription through two activation functions (AF), AF-1 in the N-terminal domain and AF-2 in the ligand binding domain. Another physiologically expressed 46 kDa ER isoform lacks the N-terminal A/B domains and is consequently devoid of AF-1. To evaluate the involvement of ER AF-1 and AF-2 in the vasculoprotective actions of estradiol (E2), we generated a targeted deletion of the ER A/B domain in the mouse named ERAF-10 mice, and a targeted deletion of amino acids 543–549 and thus deficient in AF-2 (named ERAF-20 mice). Both basal endothelial NO production was increased by E2 administration in a similar extent than in control mice. E2 similarly decreased fatty streak deposits at the aortic root from both ovariectomized 18 week-old ERAF-1+/+ LDL-r-/- (Low Density Lipoprotein receptor) and ERAF-10 LDL-r-/- mice fed with a hypercholesterolemic diet. We conclude that ER AF-1 is not required for the vasculoprotective actions of E2, whereas it is necessary for the effects of E2 on its reproductive targets. Thus, Selective Estrogen Receptor Modulators stimulating ER independently of the A/B domain and thereby with minimal activation of ER AF-1 could retain beneficial vascular actions, while minimizing the sexual effects. The results concerning ERAF-20 mice are in process and will be available at the end of 2010, and the precise role of AF2 in these actions will be presented.
Published: 2011

43. Association between adiponectin and cartilage degradation in human osteoarthritis

Author: Cécile Guillaume, Natalia Presle, Anne Abot, Jean-Yves Jouzeau, Arnaud Bianchi, Pascale Gegout-Pottie, P.-J. Francin, David Moulin, Didier Mainard, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Adult, Cartilage, Articular, Male, medicine.medical_specialty, Biomedical Engineering, Adipokine, Osteoarthritis, Chondrocyte, Dinoprostone, 03 medical and health sciences, 0302 clinical medicine, Chondrocytes, Rheumatology, Adipokines, Internal medicine, Matrix Metalloproteinase 13, medicine, Humans, Orthopedics and Sports Medicine, Obesity, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Receptor, Aggrecan, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, 0303 health sciences, Adiponectin, business.industry, Cartilage, Middle Aged, Osteoarthritis, Knee, medicine.disease, Endocrinology, medicine.anatomical_structure, Immunohistochemistry, Female, Receptors, Adiponectin, business, hormones, hormone substitutes, and hormone antagonists, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Objective: Conflicting findings raise questions about the role of adiponectin in osteoarthritis (OA). The current study aimed to investigate in OA patients the association between the production of adiponectin and the grade of cartilage destruction, and to provide functional evidence for a potential role of adiponectin in OA. Design: The expression of adiponectin was examined by immunohistochemistry in cartilage obtained from healthy individuals (n = 2; ages 56 and 41 years; 1 male and 1 female) and OA patients (n = 11; ages 64-79 years; 2 male and 9 female). The association between its production in chondrocytes and the grade of cartilage destruction was established on full-depth cartilage biopsies. The functional activity of adiponectin in OA cartilage was determined from the relation between the expression of adiponectin, its receptor, cartilage-specific components and factors involved in matrix degradation, and from the chondrocyte response to the full-length or the globular form of adiponectin. Results: Adiponectin was not detected in healthy cartilage. Conversely, the adipokine was up-regulated in damaged tissue, but no strong association with the grade of cartilage destruction was found. We showed a positive correlation between adiponectin and mPGES or MMP-13 while AdipoR1 was related to the expression of type 2 collagen, aggrecan and Sox9. The full-length form of adiponectin but not the globular isoform, stimulated the production of PGE(2) and MMP-13 activity in cultured human chondrocytes. Conclusions: The elevated level of adiponectin found in chondrocytes from OA patients might contribute to matrix remodelling during OA, the full-length isoform being the single active form. (C) 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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44. 0218: The uterine and vascular actions of estetrol delineate an original distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation

Author: Isabelle Raymond-Letron, Françoise Lenfant, Anne Abot, Shyamala S. Rajan, Aurelie J Fabre, Geoffrey L. Greene, Muriel Laine, Alain Milon, Mélanie Mestdagt, Benita S. Katzenellenbogen, Coralie Fontaine, Jean-Michel Foidart, Daniel Henrion, Romain Solinhac, Gilles Flouriot, Melissa Buscato, Anne Drougard, Jean-François Arnal, John A. Katzenellenbogen, Claude Knauf, 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), Laboratory of Tumor and Developmental Biology, Université de Liège-CHU Sart-Tilman, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Molecular and Integrative Physiology, University of Illinois System, Institut de médecine moléculaire de Rangueil (I2MR), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie des Tumeurs et du Développement), Université de Liège, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: business.industry, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Phospholipid, Uterus, Estrogen receptor, Hormone replacement therapy (menopause), 030204 cardiovascular system & hematology, Steroid, Cell biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Estetrol, medicine.anatomical_structure, chemistry, Estrogen, In vivo, Medicine, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: Estetrol (E4) is a natural estrogen produced by the human fetal liver only during pregnancy. Its distinctive biological profile offers potential benefits in women's health, such as contraception and hormone replacement therapy. The crystal structures of the estrogen receptor α (ERα) ligand binding domain with 17beta-estradiol (E2) and E4 were very similar, whereas these two estrogens showed distinct positioning within phospholipid bilayers. Using in vivo approaches, we demonstrated that high doses of E4 stimulate genomic, ERα-dependent effects in the uterus leading to epithelial proliferation and prevent atheroma in hypercholesterolemic mice to a similar extent as E2. In contrast to E2, however, E4 failed to promote membrane-initiated ERα signaling such as acceleration of endothelial healing. Moreover, E4 antagonized this endothelial effect of E2. We conclude that E4 is a weak estrogen able to modulate the nuclear/transcriptional activity of ERα, and is not only devoid of membrane-initiated steroid signal, but also able to antagonize the membrane effects of E2, thereby delineating a distinctive profile of ERα activation.
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45. Protothecosis algaemia in a patient presenting with septic arthritis: A rare case of Prototheca zopfii isolated from Malaysia

Author: Prem Ananth Palaniappan, Cassandra Anne Abot, Ratna Mohd Tap, and Fairuz Amran
Subjects: Prototheca zopfii., Protothecosis, Algaemia, Septic arthritis, Infectious and parasitic diseases, RC109-216
Abstract: Prototheca species have been reported to cause infections in human. Typically, clinical symptoms of protothecosis include cutaneous infection, olecranon bursitis, tenosynovitis and disseminated systemic disease. We report a case of septic arthritis in which Prototheca zopfii was isolated from blood. Joint aspirate was also sent for cultures but did not yield any growth. No other organisms were isolated from this patient during his admission. The blood isolate was identified to species level via Polymerase Chain Reaction (PCR) method. The patient improved with administration of intravenous itraconazole.
Published: 2021
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