Endocannabinoid synthesis and degradation, and their regulation in the framework of energy balance

Endocannabinoids are endogenous substances capable of binding to and functionally activating the two types of cannabinoid receptors identified to date, the cannabinoid receptors type 1 and 2 (CB1 and CB2 receptors). The anabolic and catabolic pathways for the two most studied endocannabinoids, N-arachidonoylethanolamine (anandamide) and 2-arachidonoyl glycerol (2- AG), have been elucidated, thus leading to the molecular characterization of some of their catabolic and biosynthetic enzymes. These proteins are hydrolytic enzymes that also recognize as substrates other congeners of anandamide and 2-AG or of their biosynthetic precursors, respectively. CB1 receptor and tissue concentrations of endocannabinoids sufficient to activate them are more widely distributed than originally believed, and are present in all brain and peripheral organs involved in the control of energy homeostasis, including the hypothalamus, nucleus accumbens, brainstem, vagus nerve, gastrointestinal trad, adipose tissue, muscle and liver. Hypothalamic and peripheral neuropeptides and hormones involved in energy balance, as well as the type of diet, regulate endocannabinoid biosynthetic and inactivating pathways, whereas endocannabinoids, in turn, regulate the expression and action of mediators involved in nutrient intake and processing. The perturbation of these cross-talks might contribute to the development of eating disorders.