The role of the endocannabinoid system in the regulation of energy expenditure.

Endocannabinoids, a lipid-derived signaling system, regulate appetite and motivation to eat via effects in the hypothalamus and nucleus accumbens. Not all the effects of endocannabinoids on fat mass can be explained by the regulation of food intake alone. Endocannabinoids and their receptors are located in areas of the central nervous system and multiple peripheral tissues involved in the regulation of intermediary metabolism and energy expenditure. In addition to regulating food intake by both central and peripherally mediated effects, endocannabinoids modify glucose and lipid metabolism so as to promote energy storage via lipogenesis and reduce energy expenditure. The endocannabinoid system appears to be overactive in obesity and may serve to maintain fat mass and underlies some of the metabolic consequences of obesity. Inhibition of the cannabinoid type-1 receptor ameliorates the effects of endocannabinoids on food intake and energy metabolism; lipogenesis is inhibited, lipolysis, fatty acid oxidation and glucose uptake increase.