Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis
2017
Chrétien, Chloé | Fenech, Claire | Liénard, Fabienne | Grall, Sylvie | Chevalier, Charlène | Chaudy, Sylvie | Brenachot, Xavier | Berges, Raymond | Louche, Katie | Stark, Romana | Nédélec, Emmanuelle | Laderrière, Amélie | Andrews, Zane B. | Benani, Alexandre | Flockerzi, Veit | Gascuel, Jean | Hartmann, Jana | Moro, Cédric | Birnbaumer, Lutz | Leloup, Corinne | Pénicaud, Luc | Fioramonti, Xavier | Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA) ; Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS) | Université de Bourgogne (UB) | Laboratoire de l'intégration, du matériau au système (IMS) ; Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS) | 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) | Monash Biomedicine Discovery Institute ; Monash University [Clayton] | Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé - Brest (UBO UFR MSS) ; Université de Brest (UBO) | Monash University [Clayton] | Institute of Clinical and Experimental Pharmacology and Toxicology ; Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE) | University of Hull [United Kingdom] | Laboratory of Neurobiology ; National Institute of Environmental Health Sciences [Durham, NC, USA] (NIEHS-NIH) ; National Institutes of Health [Bethesda, MD, USA] (NIH)-National Institutes of Health [Bethesda, MD, USA] (NIH) | Chercheur indépendant | Institut National de la Recherche Agronomique Deutsche Forschungsgemeinschaft SFB 894 TRR-152 National Institutes of Health Intramural Research Program grant Z01-ES-101684 Marie Sklodowska-Curie actions-Seventh Framework Programme (CIG NeuROSenS) PCIG09-GA-2011-293738 Societe Francophone du Diabete | ANR-11-BSV1-0007,ConnexSensing,Rôle des connexines astrocytaires dans le mécanisme de détection hypothalamique du glucose : implication sur le contrôle nerveux du métabolisme énergétique(2011)
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Show more [+] Less [-]English. The mediobasal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that transient receptor potential canonical type 3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis. To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mouse models. Hypothalamic glucose detection was studied in vivo by measuring food intake and insulin secretion in response to increased brain glucose level. The role of TRPC3 in GE neuron response to glucose was studied by using in vitro calcium imaging on freshly dissociated MBH neurons. We found that whole body and MBH TRPC3-deficient mice have increased body weight and food intake. The anorectic effect of intracerebroventricular glucose and the insulin secretory response to intracarotid glucose injection are blunted in TRPC3-deficient mice. TRPC3 loss of function or pharmacological inhibition blunts calcium responses to glucose in MBH neurons in vitro. Together, the results demonstrate that TRPC3 channels are required for the response to glucose of MBH GE neurons and the central effect of glucose on insulin secretion and food intake.
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