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RESEARCH PRODUCT

Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis

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Fil: Chrétien, Chloé. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Fenech, Claire. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Liénard, Fabienne. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Grall, Sylvie. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Chevalier, Charlène. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Chaudy, Sylvie. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Brenachot, Xavier. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Berges, Raymond. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Louche, Katie. University of Toulouse. Obesity Research Laboratory. INSERM UMR1048. Institute of Metabolic and Cardiovascular Diseases; France Fil: Stark, Romana. Monash University. Department of Physiology. Metabolic Disease and Obesity Program. Biomedicine Discovery Institute; Australia Fil: Nédélec, Emmanuelle. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Laderrière, Amélie. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Andrews, Zane B. Monash University. Department of Physiology. Metabolic Disease and Obesity Program. Biomedicine Discovery Institute; Australia Fil: Benani, Alexandre. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Flockerzi, Veit. Saarland University School of Medicine. Experimental and Clinical Pharmacology and Toxicology; Germany Fil: Gascuel, Jean. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Hartmann, Jana. Technical University Munich. Institute of Neuroscience and Center for Integrated Protein Science; Germany Fil: Moro, Cédric. University of Toulouse. Obesity Research Laboratory. INSERM UMR1048. Institute of Metabolic and Cardiovascular Diseases; France Fil: Birnbaumer, Lutz. Neurobiology Laboratory. National Institute of Environmental Health Sciences Research Triangle Park; United States Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Leloup, Corinne. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Pénicaud, Luc. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France Fil: Fioramonti, Xavier. University of Bourgogne Franche-Comté. Institut National de la Recherche Agronomique. Centre des Sciences du Goût et de l’Alimentation; France 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.