Kalsbeek Martin J T, Mulder Laurie, Yi Chun-Xia
Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam (UvA), Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Department of Endocrinology and Metabolism, Academic Medical Center (AMC), University of Amsterdam (UvA), Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Mol Cell Endocrinol. 2016 Dec 15;438:27-35. doi: 10.1016/j.mce.2016.09.028. Epub 2016 Sep 28.
Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx. Fatty acids are another source of energy for microglia and have also been shown to strongly influence microglial immune activity. Glutamine, although possibly suitable for use as an energy substrate by microglia, has been shown to have neurotoxic effects when overloaded. Microglial fuel metabolism might be associated with microglial reactivity under different pathophysiological conditions and a microglial fuel switch may thus be the underlying cause of hypothalamic dysregulation, which is associated with obesity.
小胶质细胞是中枢神经系统中的常驻巨噬细胞,负责维持健康的微环境以确保神经元存活。小胶质细胞对中枢神经系统进行不间断的巡逻,与神经元接触并寻找异常情况,所有这些都需要大量能量。在被病原体、神经元损伤或其他类型的刺激激活后,这种无信号的能量需求会增加。在三种主要能量底物——葡萄糖、脂肪酸和谷氨酰胺中,葡萄糖对小胶质细胞的存活至关重要,并且表达了几种葡萄糖转运蛋白以提供足够的葡萄糖流入。脂肪酸是小胶质细胞的另一种能量来源,并且也已显示出对小胶质细胞免疫活性有强烈影响。谷氨酰胺虽然可能适合作为小胶质细胞的能量底物,但在过载时已显示出具有神经毒性作用。在不同的病理生理条件下,小胶质细胞的燃料代谢可能与小胶质细胞的反应性相关,因此小胶质细胞的燃料转换可能是下丘脑调节失调的根本原因,而下丘脑调节失调与肥胖有关。