Endocannabinoids and related N-acylethanolamines in the control of appetite and energy metabolism: emergence of new molecular players.

PURPOSE OF REVIEW Endocannabinoids (anandamide and 2-arachidonoylgycerol) and related N-acylethanolamines (N-oleoylethanolamine) exhibit opposite effects in the control of appetite. The purpose of this review is to highlight the similarities and differences of three major lipid-signaling molecules by focusing on their mode of action and the proteins involved in the control of food intake and energy metabolism. RECENT FINDINGS Anandamide and 2-arachidonoylglycerol promote food intake and are the main endogenous ligands of the cannabinoid receptors. One of them, the cannabinoid receptor 1, is responsible for the control of food intake and energy expenditure both at a central and a peripheral level, affecting numerous anorexigenic and orexigenic mediators (leptin, neuropeptide Y, ghrelin, orexin, endogenous opioids, corticotropin-releasing hormone, alpha-melanocyte stimulating hormone, cocaine and amphetamine-related transcript). In the gut, N-oleoylethanolamine plays an opposite role in food regulation, by interacting with two molecular targets different from the cannabinoid receptors: the nuclear receptor peroxisome proliferator-activated receptor alpha and a G-protein coupled receptor GPR119. SUMMARY Recent findings on the molecular mechanisms underlying the promotion of food intake or, in contrast, the suppression of food intake by anandamide and N-oleoylethanolamine, are summarized. Potential strategies for treating overweight, metabolic syndrome, and type II diabetes are briefly outlined.