Brain control of energy homeostasis: Implications for anti-obesity pharmacotherapy

Despite the evolution of hardwired homeostatic mechanisms to balance food intake with energy needs, the obesity epidemic continues to escalate globally. However, recent breakthroughs in delineating the molecular signaling pathways by which neural circuits regulate consummatory behaviors, along with transformative advances in peptide-based pharmacotherapy, are fueling the development of a new generation of safe and effective treatments for obesity. Here, we outline our current understanding of how the central nervous system controls energy homeostasis and examine how emerging insights, including those related to neuroplasticity, offer new perspectives for restoring energy balance and achieving durable weight loss. Together, these advances provide promising avenues for treating obesity and managing cardiometabolic disease.