Microglia play a crucial role in immune responses, including inflammation. Diet-induced obesity (DIO) triggers microglia activation and hypothalamic inflammation as early as 3 days after high-fat diet (HFD) exposure, before changes in body weight occur. The intracellular mechanism(s) responsible for HFD-induced microglia activation is ill defined. Here, we show that in vivo, HFD induced a rapid and transient increase in uncoupling protein 2 (Ucp2) mRNA expression together with changes in mitochondrial dynamics. Selective microglial deletion of Ucp2 prevented changes in mitochondrial dynamics and function, microglia activation, and hypothalamic inflammation. In association with these, male and female mice were protected from HFD-induced obesity, showing decreased feeding and increased energy expenditure that were associated with changes in the synaptic input organization and activation of the anorexigenic hypothalamic POMC neurons and astrogliosis. Together, our data point to a fuel-availability-driven mitochondrial mechanism as a major player of microglia activation in the central regulation of DIO.

中文翻译：

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小胶质UCP2介导高脂喂养引起的炎症和肥胖。

小胶质细胞在包括炎症在内的免疫反应中起着至关重要的作用。饮食诱发的肥胖（DIO）最早在高脂饮食（HFD）暴露后三天（体重发生变化之前）触发小胶质细胞活化和下丘脑炎症。导致HFD诱导的小胶质细胞活化的细胞内机制尚不明确。在这里，我们显示体内，HFD诱导解偶联蛋白2（Ucp2）mRNA表达快速和瞬时增加以及线粒体动力学变化。Ucp2的选择性小胶质细胞的删除阻止线粒体动力学和功能，小胶质细胞激活和下丘脑炎症的变化。与之相关的是，雄性和雌性小鼠受到了HFD诱导的肥胖的保护，表现出与突触输入组织的变化以及食欲减退的下丘脑POMC神经元的激活和星形胶质细胞增生相关的进食减少和能量消耗增加。总之，我们的数据表明，由燃料可用性驱动的线粒体机制是DIO中央调节中小胶质细胞激活的主要参与者。