Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function.
Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function.
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DOI：
10.1016/j.celrep.2014.11.018
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发表时间：
2014-12-24
期刊：
影响因子：
8.8
通讯作者：
Koliwad SK
中科院分区：
文献类型：
--
作者：
Valdearcos M;Robblee MM;Benjamin DI;Nomura DK;Xu AW;Koliwad SK
富含饱和脂肪的饮食会导致下丘脑内侧基底核（MBH）的炎症、神经胶质增生和神经元应激。在这里，我们表明，小胶质细胞介导这一过程及其功能的影响。尽管小胶质细胞和星形胶质细胞在喂食富含饱和脂肪酸（SFA）的饮食的小鼠的MBH中积累，但只有小胶质细胞经历炎症活化，沿着下丘脑SFA的积累。肠灌胃特别是与SFA再现小胶质细胞活化和神经元应激的MBH，和SFA治疗激活小鼠小胶质细胞，但不是星形胶质细胞，在文化。此外，消耗小胶质细胞消除SFA诱导的下丘脑切片炎症。值得注意的是，从小鼠的MBH中消耗小胶质细胞消除了由过量SFA消耗诱导的炎症和神经元应激，并且在这种情况下，小胶质细胞消耗增强了瘦素信号传导并减少了食物摄入。因此，我们表明，小胶质细胞的意义SFA和精心策划的MBH，改变神经元功能时，SFA消耗高的炎症过程。
Diets rich in saturated fat produce inflammation, gliosis, and neuronal stress in the mediobasal hypothalamus (MBH). Here we show that microglia mediate this process and its functional impact. Although microglia and astrocytes accumulate in the MBH of mice fed a diet rich in saturated fatty acids (SFAs), only the microglia undergo inflammatory activation, along with a build-up of hypothalamic SFAs. Enteric gavage specifically with SFAs reproduces microglial activation and neuronal stress in the MBH, and SFA treatment activates murine microglia, but not astrocytes, in culture. Moreover, depleting microglia abrogates SFA-induced inflammation in hypothalamic slices. Remarkably, depleting microglia from the MBH of mice abolishes inflammation and neuronal stress induced by excess SFA consumption, and in this context, microglial depletion enhances leptin signaling and reduces food intake. We thus show that microglia sense SFAs and orchestrate an inflammatory process in the MBH that alters neuronal function when SFA consumption is high.