Lipid endocannabinoids in energy metabolism, stress and developmental programming

The endocannabinoid system (ECS) regulates brain development and function, energy metabolism and stress in a sex-, age- and tissue-dependent manner. The ECS comprises mainly the bioactive lipid ligands anandamide (AEA) and 2-aracdonoylglycerol (2-AG), cannabinoid receptors 1 and 2 (CB1 and CB2), and several metabolizing enzymes. The endocannabinoid tonus is increased in obesity, stimulating food intake and a preference for fat, reward, and lipid accumulation in peripheral tissues, as well as favoring a positive energy balance. Energy balance and stress responses share adaptive mechanisms regulated by the ECS that seem to underlie the complex relationship between feeding and emotional behavior. The ECS is also a key regulator of development. Environmental insults (diet, toxicants, and stress) in critical periods of developmental plasticity, such as gestation, lactation and adolescence, alter the ECS and may predispose individuals to the development of chronic diseases and behavioral changes in the long term. This review is focused on the ECS and the developmental origins of health and disease (DOHaD).