The endocannabinoid system is a major player in energy balance regulation.
Soutenue le 4 mars 2013
– Abstract : The endocannabinoid system is a major player in energy balance regulation.
However, a complete understanding of its role within the hypothalamus, a region critically involved in energy balance regulation, is still missing. The general aim of this PhD work was to dissect the specific role of the cannabinoid type 1 receptor (CB1) expressed on different hypothalamic neuronal populations in energy balance regulation and glucose homeostasis by characterizing three new mouse mutant lines with a conditional deletion of CB1.
On standard diet, CB1 deletion within the hypothalamus induced an increase in energy expenditure and a decrease in body weight gain without modifying food intake, while CB1 deletion within the ventromedial nucleus of the hypothalamus (VMN-CB1-KO) decreased fat mass, increased fatty acid oxidation in vivo and sympathetic nervous system (SNS) activity, and improved peripheral glucose metabolism. CB1 deletion within the paraventricular nucleus of the hypothalamus (PVN-CB1-KO) decreased body weight gain without affecting food intake or body composition. When exposed to a high-fat diet, VMN-CB1-KO mice gained significantly more weight and fat mass than their WT, while PVN-CB1-KO mice were partly protected from diet-induced obesity thanks to increased energy expenditure. These results overall suggest that CB1 expressed on different hypothalamic neuronal populations have distinct roles in energy balance regulation, which in turn also depend on the diet consumed.
Key words: Hypothalamus, CB1, energy balance, leptin, high-fat diet
Sophie LAYE DR INRA UMR 1286, Bordeaux, Président
Sébastien BOURET Group leader, Los Angeles CR CNRS, Inserm U837, Lille, Rapporteur
Patricia PARNET,DR INRA UMR 1280, Nantes, Rapporteur
Philippe CIOFI, CR INSERM U862, Bordeaux, Examinateur
Uberto PAGOTTO, MD-PhD, Université de Bologne, Examinateur
Daniela Cota, CR, INSERM U862, Bordeaux, Directeur de thèse