研究人员发现在体内，HFD引起Ucp2（uncoupling protein 2）mRNA快速、短暂的表达增加以及线粒体动态的变化。在小胶质细胞中选择性敲除Ucp2阻止了线粒体动态与功能、小胶质细胞激活以及下丘脑炎症等方面的变化。与这些相关联，保护雄性和雌性小鼠免受高脂肪饮食（HFD）诱导的肥胖，显示出摄食的减少和能量消耗的增加，其与突触输入信号的组织和厌食性下丘脑POMC神经元和星形胶质细胞增生的激活等方面的改变相关。总之，这些数据表明能量可用性驱动的线粒体机制是小胶质细胞激活是饮食诱导肥胖（DIO）中枢调节的主要参与者。
Abstract: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.