This report by Vincenzo Di Marzo reviews the endocannabinoid (EC) signalling system and its components (ECs, EC anabolic and catabolic enzymes, and cannabinoid receptors). It also describes the system’s important role as a regulator of lipid and glucose metabolism at several levels, with the possible endpoint of the accumulation of energy as fat. The author explains how dysregulation of the EC system, following positive energy balance, might contribute to excessive intra-abdominal (visceral) fat accumulation and reduced adiponectin release from this fat depot as well as the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes. As proposed by the author, this phenomenon may possibly explain the mechanism of action of cannabinoid receptor antagonists recently developed by the pharmaceutical industry to complement lifestyle modification for weight reduction, glycemic control, and dyslipidemia in obese and type 2 diabetic patients. The author recognized that additional studies are needed to fully understand the role, regulation, and dysregulation of ECs in the skeletal muscle, liver, and pancreas and to examine the relationship between the EC system and hormones that control metabolism (insulin, gastrointestinal neuropeptides). According to the author, these studies should help strengthen the notion that cannabinoid receptor antagonists have a weight loss-independent beneficial metabolic effect and facilitate the identification of the “right patient” for this type of treatment.
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