Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, 85764 Neuherberg, Germany.
German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Int J Mol Sci. 2021 Jun 8;22(12):6176. doi: 10.3390/ijms22126176.
Astrocytes are a type of glial cell anatomically and functionally integrated into the neuronal regulatory circuits for the neuroendocrine control of metabolism. Being functional integral compounds of synapses, astrocytes are actively involved in the physiological regulatory aspects of metabolic control, but also in the pathological processes that link neuronal dysfunction and obesity. Between brain areas, the hypothalamus harbors specialized functional circuits that seem selectively vulnerable to metabolic damage, undergoing early cellular rearrangements which are thought to be at the core of the pathogenesis of diet-induced obesity. Such changes in the hypothalamic brain region consist of a rise in proinflammatory cytokines, the presence of a reactive phenotype in astrocytes and microglia, alterations in the cytoarchitecture and synaptology of hypothalamic circuits, and angiogenesis, a phenomenon that cannot be found elsewhere in the brain. Increasing evidence points to the direct involvement of hypothalamic astrocytes in such early metabolic disturbances, thus moving the study of these glial cells to the forefront of obesity research. Here we provide a comprehensive review of the most relevant findings of molecular and pathophysiological mechanisms by which hypothalamic astrocytes might be involved in the pathogenesis of obesity.
星形胶质细胞是一种神经胶质细胞，在解剖学和功能上与神经元调节回路整合在一起，用于神经内分泌代谢的控制。作为突触的功能整合化合物，星形胶质细胞积极参与代谢控制的生理调节方面，也参与将神经元功能障碍与肥胖联系起来的病理过程。在脑区之间，下丘脑具有专门的功能回路，这些回路似乎容易受到代谢损伤的影响，经历早期的细胞重排，这被认为是饮食诱导肥胖发病机制的核心。下丘脑脑区的这种变化包括促炎细胞因子的增加、星形胶质细胞和小胶质细胞中存在反应性表型、下丘脑回路的细胞结构和突触发生改变以及血管生成，这种现象在大脑的其他部位都不存在。越来越多的证据表明，下丘脑星形胶质细胞直接参与了这种早期代谢紊乱，因此，研究这些神经胶质细胞成为肥胖研究的前沿。在这里，我们提供了一个全面的综述，介绍了分子和病理生理学机制的最相关发现，这些机制可能涉及下丘脑星形胶质细胞在肥胖发病机制中的作用。
