CB1 cannabinoid receptor determines metabolic responses to diet and leptin
In this recent publication, Daniela Cota's group shows that CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin, therefore demonstrating that CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.
Metabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN) participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1) receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1) decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.
Pierre Cardinal, Caroline Andre?, Carmelo Quarta, Luigi Bellocchio, Samantha Clark , Melissa Elie, Thierry Leste-Lasserre, Marlene Maitre, Delphine Gonzales, Astrid Cannich, Uberto Pagotto, Giovanni Marsicano, Daniela Cota. CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin.Molecular Metabolism (2014) 1e12, 2014