Daniela Cota, Pierre Cardinal et al. inEndocrinology

Cannabinoid type 1 (CB1) receptors on Sim1-expressing neurons regulate energy expenditure in male mice. Cardinal P, Bellocchio L, Guzmán-Quevedo O, André C, Clark S, Elie M, Leste-Lasserre T, Gonzales D, Cannich A, Marsicano G, Cota D.
Endocrinology. 2014 Dec 2:en20141437

Endocannabinoids, by acting on the cannabinoid type 1 (CB₁) receptor, are known to exert a regulatory control on essentially every aspect related to the search, intake, metabolism and storage of calories. In particular, while activation of the CB₁ receptor generally increases body weight, complete genetic deletion or pharmacological blockade of this receptor inhibits body weight gain and protects from obesity. Consequently, the CB₁ receptor is nowadays considered a potential pharmacotherapeutic target for obesity, diabetes and metabolic disorders.

The hypothalamus is one of the major brain structures regulating energy balance. However, whether specific hypothalamic nuclei or neuronal populations determine CB₁ receptor-dependent effects on food intake and body weight remains poorly understood. Among other hypothalamic nuclei, the paraventricular nucleus (PVN) plays important roles in the regulation of energy balance through the control of neuroendocrine and hormonal responses as well as of energy expenditure and thermogenesis.

In this study, by deleting the CB₁ receptor from single-minded 1 (Sim1) neurons, which constitute the majority of neurons of the PVN, we demonstrate that CB₁ receptor signaling in PVN neurons leads to obesity and insulin resistance by hindering energy expenditure and thermogenesis, likely via the modulation of the sympathetic nervous system. This effect however depends upon the diet consumed, since while Sim1-CB₁-KO mice fed a high-fat diet gain less weight and have better insulin sensitivity than WT control mice, no phenotypic differences are observed when Sim1-CB₁-KO and their WT littermates are fed a standard chow.

We conclude that CB₁ receptor signaling on Sim1 neurons plays a key role in favoring body weight gain during consumption of an obesogenic, calorically rich diet, by altering sympathetic nervous system activity and consequently energy expenditure.

Daniela Cota

Last update on 07.01.2015

First author

Pierre Cardinal
Post doc
Team Denis Richard
Laval University
Quebec 

Daniela Cota, MD
Group Leader, Group “Energy Balance and Obesity”
Associate Director NeuroCentre Magendie. INSERM U862, Bordeaux University . NeuroCentre Magendie