Nguyen Linda T, Dodd Garron T
The University of Melbourne, Department of Anatomy and Physiology, Melbourne, VIC, Australia.
NPJ Metab Health Dis. 2024 Oct 4;2(1):27. doi: 10.1038/s44324-024-00026-1.
Metabolic diseases such as obesity and type 2 diabetes affect >2 billion people worldwide, yet there are currently no effective treatments to promote remission of disease. It is therefore critical to understand the physiological and pathophysiological mechanisms underlying metabolic disease, to drive the development of effective therapeutics. Whilst the majority of research over the past few decades has focused on neurons in the hypothalamus, there is growing evidence that non-neuronal glial cells in this region play a substantial role in regulating metabolism. Here, we provide an overview of the current dogmatic view of the neuroendocrine axis governing metabolism and update this neuron-centric view to include emerging evidence implicating glial cells including tanycytes, astrocytes, microglia, and oligodendrocyte lineage cells. We discuss the latest research implicating glia in hormone transport and hypothalamic inflammation, highlighting these cells as key contributors to metabolic control and dysfunction. Glial cells therefore offer new cellular and molecular targets for future therapeutic design, to tackle metabolic disease treatment from a new perspective.
肥胖和2型糖尿病等代谢性疾病影响着全球超过20亿人,但目前尚无有效的治疗方法来促进疾病缓解。因此,了解代谢性疾病背后的生理和病理生理机制对于推动有效治疗方法的开发至关重要。尽管过去几十年的大部分研究都集中在下丘脑的神经元上,但越来越多的证据表明,该区域的非神经元胶质细胞在调节新陈代谢中发挥着重要作用。在此,我们概述了当前关于调节新陈代谢的神经内分泌轴的传统观点,并更新了这种以神经元为中心的观点,纳入了涉及胶质细胞(包括伸长细胞、星形胶质细胞、小胶质细胞和少突胶质细胞谱系细胞)的新证据。我们讨论了有关胶质细胞参与激素运输和下丘脑炎症的最新研究,强调这些细胞是代谢控制和功能障碍的关键因素。因此,胶质细胞为未来的治疗设计提供了新的细胞和分子靶点,以便从新的角度解决代谢性疾病的治疗问题。