The endocannabinoid system: directing eating behavior and macronutrient metabolism

Bruce A. Watkins, Jeffrey Kim

For many years, the brain has been the primary focus for research on eating behavior. More recently, the discovery of the endocannabinoids (EC) and the endocannabinoid system (ECS), as well as the characterization of its actions on appetite and metabolism, has provided greater insight on the brain and food intake. The purpose of this review is to explain the actions of EC in the brain and other organs as well as their precursor polyunsaturated fatty acids (PUFA) that are converted to these endogenous ligands. The binding of the EC to the cannabinoid receptors in the brain stimulates food intake, and the ECS participates in systemic macronutrient metabolism where the gastrointestinal system, liver, muscle, and adipose are involved. The EC are biosynthesized from two distinct families of dietary PUFA, namely the n-6 and n-3. Based on their biochemistry, these PUFA are well known to exert considerable physiological and health-promoting actions. However, little is known about how these different families of PUFA compete as precursor ligands of cannabinoid receptors to stimulate appetite or perhaps down-regulate the ECS to amend food intake and prevent or control obesity. The goal of this review is to assess the current available research on ECS and food intake, suggest research that may improve the complications associated with obesity and diabetes by dietary PUFA intervention, and further reveal mechanisms to elucidate the relationships between substrate for EC synthesis, ligand actions on receptors, and the physiological consequences of the ECS. Dietary PUFA are lifestyle factors that could potentially curb eating behavior, which may translate to changes in macronutrient metabolism, systemically and in muscle, benefiting health overall.