Johansen Valdemar Brimnes Ingemann, Petersen Jonas, Lund Jens, Mathiesen Cecilie Vad, Fenselau Henning, Clemmensen Christoffer
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Cell. 2025 Aug 7;188(16):4178-4212. doi: 10.1016/j.cell.2025.06.010.
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.
尽管机体存在固有的稳态机制来平衡食物摄入与能量需求，但全球肥胖流行仍在持续加剧。然而，在描绘神经回路调节进食行为的分子信号通路方面的最新突破，以及基于肽的药物治疗方面的变革性进展，正推动着新一代安全有效的肥胖治疗方法的开发。在此，我们概述了目前对中枢神经系统如何控制能量稳态的理解，并探讨了包括与神经可塑性相关的见解在内的新认识如何为恢复能量平衡和实现持久体重减轻提供新的视角。这些进展共同为治疗肥胖和管理心脏代谢疾病提供了有前景的途径。
