A role for the endocannabinoid system in obesity

Abstract

Endocannabinoids are the endogenous ligands for the cannabinoid receptors type 1 and 2. These membrane receptors are responsible for the psychotropic effects of Cannabis Sativa, when bound to its active component known as (-)-Delta(9)-tetrahydro-cannabinol. Cannabinoid receptors, endocannabinoids and the enzymes catalyzing their biosynthesis and degradation, constitute the endocannabinoid system (ECS), which has a remarkable role controlling energy balance, both at central nervous system and peripheral tissues. The ECS regulates food ingestion by stimulating a network of orexigenic neurons present in the hypothalamus and reinforcing motivation and reward to food consumption in the nucleus accumbens. Regarding peripheral tissues, this system controls lipid and glucose metabolism at different levels, reduces energy expenditure and leads energy balance to fat storage. Metabolic alterations, including excessive accumulation of abdominal fat, dyslipidaemia and hyperglicaemia, are suggested to be associated to a hyperactivated ECS. Since obesity is one of the major health problems in modern societies, in this review we discuss the role of the endocannabinoid system in metabolic pathways associated to control mechanisms of energy balance and its involvement in overweight and obesity. In addition, we also discuss therapeutic possibilities and emergent problems due to cannabinoid receptor type 1 antagonism utilized as treatment for such alterations.