title: Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis.
abstract: 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.
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Chrétien
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Fenech
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Liénard
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Grall
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Charlène
authors.initials: C
authors.lastname: Chevalier
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chaudy
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Brenachot
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Berges
authors.affiliation: INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, Obesity Research Laboratory, University of Toulouse, Toulouse, France.
authors.forename: Katie
authors.initials: K
authors.lastname: Louche
authors.affiliation: Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Department of Physiology, Monash University, Clayton, VIC, Australia.
authors.forename: Romana
authors.initials: R
authors.lastname: Stark
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Nédélec
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Laderrière
authors.affiliation: Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Department of Physiology, Monash University, Clayton, VIC, Australia.
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benani
authors.affiliation: Experimental and Clinical Pharmacology and Toxicology, Saarland University School of Medicine, Homburg, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Flockerzi
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Gascuel
authors.affiliation: Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, Munich, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Hartmann
authors.affiliation: INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, Obesity Research Laboratory, University of Toulouse, Toulouse, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Moro
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC.|Institute of Biomedical Research, Catholic University of Argentina, Buenos Aires, Argentina.
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Leloup
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
authors.affiliation: Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France xavier.fioramonti@inra.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fioramonti
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics*; D004435:Eating / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D005215:Fasting; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D007328:Insulin; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D005947:Glucose