A pipeline for identification and validation of brain targets for weight loss

Abstract

Obesity, a major risk factor for cardiometabolic diseases and various forms of cancer, represents one of the greatest health challenges of the modern world. While the relative contributions of genetic, socioeconomic and dietary factors remain controversial, recent progress in our understanding of the biological pathways controlling appetite and energy balance offer new prospects of curbing the obesity epidemic. Unlike the first generation of anti-obesity drugs that failed to combine safety and efficacy, a new class of anti-obesity agents leveraging the appetite-suppressing effect of GLP-1R agonism has emerged, producing spectacular weight loss profiles in obese patients. This has catalysed a renewed interest in the discovery of anti-obesity drugs and highlighted the need to identify drug combinations to further increase weight loss responses to GLP-1 receptor agonists, alternative drugs treating forms of obesity that do not respond to incretin-based therapies, and strategies for long-term weight loss maintenance.