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

Didier M. Lambert and Giulio G. Muccioli

Current Opinion in Clinical Nutrition and Metabolic Care (2007) 10:735-744

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, a-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 a 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.
Keywords
2-arachidonoylglycerol, anandamide, CB1 cannabinoid receptor, GPR-119, oleoylethanolamide, peroxisome
proliferator activated receptor-a