Role of the endocannabinoid system in metabolic control

Jun Wang, Natsuo Ueda
Current Opinion in Nephrology and Hypertension 2008, 17 (1): 1-10

PURPOSE OF REVIEW: Growing evidence suggests an important role in metabolic control of the endocannabinoid system, which is composed of cannabinoid receptors, endocannabinoids, and related enzymes. In this short review, we describe the latest advances in this research field, including the antiobesity effect of the cannabinoid receptor CB1 antagonist rimonabant and the anorexic effect of N-oleoylethanolamine, an endocannabinoid-related, endogenous substance.

RECENT FINDINGS: CB1 is expressed not only in various brain regions, including hypothalamus, but also in peripheral organs such as adipose tissue and liver. The endocannabinoid system appears to function as a physiological system regulating food intake, energy balance, and lipid metabolism through both central and peripheral mechanisms. Obesity may be associated with hyperactivity of the endocannabinoid system. Large phase III trials of rimonabant confirmed significant weight loss and waist circumference reduction in overweight and obese patients. The levels of HDL-cholesterol, triglycerides, and HbA1c were also improved. The anorexic effect of N-oleoylethanolamine was suggested to be mediated by peroxisome proliferator-activated receptor-alpha and the G protein-coupled receptor GPR119.

SUMMARY: These results highlight the importance of an endocannabinoid tone in metabolic control and therapeutic usefulness of CB1 antagonists. Derivatives of N-oleoylethanolamine may be developed as new antiobesity drugs.

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