Endocannabinoids and obesity development – the adipose tissue

The adipose tissue is an endocrine organ with a key role in energy metabolism. The expansion of body fat (particularly of visceral fat) contributes to the increased cardiovascular risk of obese individuals. Obesity and its metabolic complications are characterized by fat inflammation and by an overactive endocannabinoid (EC) system. Chronic treatment with cannabinoid receptor type 1 (CB1R) antagonists leads to weight loss and improved cardiometabolic risk profile in obese rodents and humans. EC overactivity is a cause of mitochondrial dysfunction, which may trigger endoplasmic reticulum stress in adipocytes and metabolically active organs, thus significantly contributing to the pathogenesis and progression of obesity. Among the major pathways involved in these processes, the nitric oxide-generating system and the p38 MAPK pathways might be targets for the development of anti-obesity drugs. Peripheral CB1Rs, and possibly CB2Rs, also play significant roles in obesity and diabetes. Together, these findings support the concept that dietary/lifestyle interventions and pharmacologic compounds, able to attenuate EC overactivity in adipose and other metabolically active tissues, may be useful for the treatment of human obesity and related disorders.