Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, 50931 Cologne, Germany.
Policlinic for Endocrinology, Diabetes, and Preventive Medicine (PEDP), University Hospital Cologne, 50924 Cologne, Germany.
Science. 2023 Sep 29;381(6665):eabl7398. doi: 10.1126/science.abl7398.
Systemic metabolism has to be constantly adjusted to the variance of food intake and even be prepared for anticipated changes in nutrient availability. Therefore, the brain integrates multiple homeostatic signals with numerous cues that predict future deviations in energy supply. Recently, our understanding of the neural pathways underlying these regulatory principles-as well as their convergence in the hypothalamus as the key coordinator of food intake, energy expenditure, and glucose metabolism-have been revealed. These advances have changed our view of brain-dependent control of metabolic physiology. In this Review, we discuss new concepts about how alterations in these pathways contribute to the development of prevalent metabolic diseases such as obesity and type 2 diabetes mellitus and how this emerging knowledge may provide new targets for their treatment.
全身代谢必须不断适应食物摄入的变化,甚至要为营养物质可用性的预期变化做好准备。因此,大脑整合了多种稳态信号和大量提示,以预测未来能量供应的偏差。最近,我们对这些调节原则的神经通路以及它们在下丘脑的汇聚有了更多的了解,而下丘脑是调节食物摄入、能量消耗和葡萄糖代谢的关键协调器。这些进展改变了我们对大脑依赖性控制代谢生理学的看法。在这篇综述中,我们讨论了这些途径的改变如何导致肥胖和 2 型糖尿病等常见代谢疾病的发展的新概念,以及这一新兴知识如何为这些疾病的治疗提供新的靶点。