The role of the endocannabinoid system in lipogenesis and fatty acid metabolism

Endocannabinoids (ECs) regulate energy balance by modulating hypothalamic circuits controlling food intake and energy expenditure. However, convincing evidence has accumulated indicating that the EC system is present also in peripheral tissues, in particular in adipose tissue. Fat cells produce and are targets of ECs. Glucose uptake and lipoprotein lipase (LPL) activity, lipogenesis and adipogenesis are stimulated by ECs through cannabinoid 1 (CB1) receptors. Moreover, CB1 activation leads to a decreased mitochondrial biogenesis and function through inhibition of endothelial nitric oxide synthase (eNOS). All these effects are blocked by the CB1 antagonist rimonabant, suggesting that the weight-reducing effect of CB1 blockade is due not only to the transient suppression of food intake and reduction of lipogenesis but also to an increased mitochondrial biogenesis and oxidative metabolism which counteracts the inhibitory effects of ECs, levels of which are increased in fat tissues of obese rodents and humans. This review focuses on the role of ECs in adipose tissue metabolism, adipokine production, and interactions between ECs and peroxisome proliferator-activated receptors (PPARs) during adipogenesis.

Keywords: endocannabinoids, 2-arachidonoylglycerol, anandamide, CB1 receptor, adipose tissue, mitochondrial biogenesis, rimonabant, CB1 receptor knock-out mice