CB1 cannabinoid receptor in SF1-expressing neurons of the ventromedial hypothalamus determines metabolic responses to diet and leptin

Abstract 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. C...

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Bibliographic Details
Published in:Molecular metabolism (Germany) 2014-10, Vol.3 (7), p.705-716
Main Authors: Cardinal, Pierre, André, Caroline, Quarta, Carmelo, Bellocchio, Luigi, Clark, Samantha, Elie, Melissa, Leste-Lasserre, Thierry, Maitre, Marlene, Gonzales, Delphine, Cannich, Astrid, Pagotto, Uberto, Marsicano, Giovanni, Cota, Daniela
Format: Article
Language:English
Subjects:
CB1 receptor
Endocannabinoid
Endocrinology & Metabolism
Hypothalamus
Leptin
Obesity
Original
Ventromedial nucleus
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Summary:Abstract 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.
ISSN:2212-8778
2212-8778
DOI:10.1016/j.molmet.2014.07.004