Beyond the Scale: Exploring the Endocannabinoid System's Impact on Obesity.

Purpose of review: This review explores the role of the endocannabinoid system (ECS) in regulating energy balance, food intake, and metabolism, with a focus on how ECS dysregulation contributes to obesity. The goal is to provide insights into the mechanisms underlying obesity and its associated metabolic disorders.

Recent findings: Recent research indicates that the ECS significantly influences food intake, fat storage, insulin sensitivity, and inflammation, all of which are central to the development and progression of obesity. New research areas include the interaction between the ECS and gut microbiota, circadian rhythms of the ECS, and the impact of genetic and epigenetic factors on ECS function. Interest in the therapeutic potential of targeting the ECS has grown, with earlier treatments like CB1 receptor antagonists showing mixed results in efficacy and safety. Evidence from both animal and human studies highlight the impact of elevated levels of the endocannabinoids anandamide and 2-AG on food intake, insulin resistance, visceral fat accumulation, and metabolic disturbances associated with obesity. The review explores the interaction between the ECS and other physiological systems, including gut-brain communication, circadian rhythms, as well as leptin and ghrelin signaling. Additionally, genetic and epigenetic factors influencing ECS function are examined, emphasizing their contribution to obesity susceptibility. While therapeutic approaches targeting the ECS, particularly CB1 receptor antagonism, have shown potential in managing obesity, the review acknowledges the challenges posed by central nervous system side effects in earlier treatments like rimonabant. However, recent advancements in peripherally restricted CB1 antagonists offer renewed hope for safer and more effective obesity treatments. The review concludes by addressing future research directions and therapeutic strategies to combat this global health challenge.