Transient receptor potential canonical 3 (TRPC3) channels are required for hypothalamic glucose detection and energy homeostasis

Chloe Chretien, Claire Fenech, Fabienne Lienard, Sylvie Grall, Charlene Chevalier, Sylvie Chaudy, Xavier Brenachot, Raymond Berges, Katie Louche, Romana Stark, Emmanuelle Nedelec, Amelie Laderriere, Zane B. Andrews, Alexandre Benani, Veit Flockerzi, Jean Gascuel, Jana Hartmann, Cedric Moro, Lutz Birnbaumer, Corinne LeloupLuc Penicaud, Xavier Fioramonti

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26 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)314-324
Number of pages11
Issue number2
Publication statusPublished - Feb 2017

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