小胶质细胞
神经炎症
脂滴
脂质代谢
细胞生物学
生物
基因剔除小鼠
条件基因敲除
脂解
缺氧(环境)
自噬
体外
脂质积聚
神经科学
运动前神经元活动
胶质增生
脂质信号
前脑
神经胶质
脂肪酶
生物化学
突变体
中枢神经系统
作者
Wenyu Hu,Shuoshuo Li,Wenjun Shi,Ping Zhang,Xue Zhang,Ying Liu,Xin Zhou,Peng Shi,Junliang Yuan,Zengqiang Yuan,Jinbo Cheng
出处
期刊:Glia
[Wiley]
日期:2025-12-12
卷期号:74 (2): e70118-e70118
摘要
Exposure to hypoxic environments leads to neurological dysfunction, with recent studies implicating microglia-derived neuroinflammation involved in hypoxia-induced neuronal impairment. However, the underlying pathological mechanisms remain largely unclear. Lipid-droplet-accumulating microglia (LDAM) have been linked to age-related and genetic forms of neurodegeneration, prompting the investigation of their role in hypoxia-induced neuronal impairment. In this study, we observed that hypoxia induced lipid droplets accumulation in microglia, accompanied by increased levels of RETSAT, an enzyme involved in lipid metabolism regulation. Conditional knockout of RETSAT in microglia decreased lipid droplets accumulation and alleviates hypoxia-induced microglial-derived neuroinflammation and oxidative stress, both in vitro and in vivo. Our biological studies indicate that the beneficial effects of RETSAT knockout on lipid droplets degradation are primarily mediated through enhanced activity of hormone-sensitive lipase (HSL). Furthermore, we found that the hypoxic adaptation-related RETSAT mutation Q247R promotes microglia lipolysis under hypoxic conditions. These findings suggest that RetSat is a potential therapeutic target for the prevention and treatment of hypoxia-induced microglial activation.
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