过剩的脂肪酸合成会增加脂肪细胞中的氧化应激,并导致脂质缩
Li Weng1,2, Wen-Shuai Tang1, Xu Wang3
1State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Drug Clinical Trial Center, Shanghai Xuhui Central Hospital / Zhongshan-Xuhui Hospital, Zhongshan Hospital, Fudan University, Shanghai, China.
Nature communications
|January 3, 2024
概括
脂肪细胞中过度的脂肪酸合成会引发细胞死亡和脂质缩. 抑制ROS的产生为获得性脂质营养不良提供了一个潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 代谢疾病 代谢疾病
- 分子内分泌学分子内分泌学
背景情况:
- 脂肪细胞对于脂肪酸储存至关重要,但它们的内源性脂肪酸合成率在生理上很低.
- 这种低合成率的根本原因及其对脂肪细胞健康的影响尚未完全理解.
研究的目的:
- 为了研究脂肪细胞脂肪酸合成升高的后果.
- 确定脂肪酸合成的分子调节剂及其在脂肪细胞功能障碍和脂质变中的作用.
- 探索针对脂质变的活性氧物种 (ROS) 的治疗潜力.
主要方法:
- 研究了脂肪酸合成酶 (FASN) 在脂肪细胞功能中的作用.
- 利用转录分析和分子分析来研究细胞机制.
- 产生并分析了特定脂肪细胞的雄性Med20淘汰赛小鼠.
- 在小鼠模型和一个患有脂质营养不良的人类患者中评估了ROS清理的影响.
主要成果:
- 增加的FASN转录提高脂肪酸合成,耗尽NADPH,并增强ROS产量,诱导脂肪细胞亡.
- 确定MED20是FASN转录的负调节者.
- 脂肪细胞中的Med20缺乏导致小鼠的渐进性脂质变,这种情况通过ROS清理得到改善.
- 在与艾滋病毒相关的脂质缩和人类患者的小鼠模型中,ROS中和改善了代谢障碍.
结论:
- 脂肪细胞中多余的脂肪酸合成驱动了通过ROS生成的亡和脂质变.
- MED20作为FASN的关键负调节剂,控制脂肪细胞脂质代谢.
- 向ROS为管理获得性脂质营养不良和相关代谢并发症提供了一个有希望的治疗途径.
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