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脂肪细胞NADH脱酶逆转昼夜和饮食诱导的代谢综合征

Chelsea Hepler^1,2, Nathan J Waldeck³, Benjamin J Weidemann³

¹Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. hepler@umich.edu.

Nature metabolism

|February 18, 2026

概括

循环时钟通过线粒体复合体I呼吸来调节脂肪细胞代谢. 破坏这个时钟会损害代谢健康,但恢复复合体I功能提供了保护.

科学领域:

生物化学生物化学
代谢过程中的代谢.
时间生物学时间生物学

背景情况:

由转录-翻译反循环驱动的循环时钟 (例如,CLOCK,BMAL1,PER,CRY) 管理日常节律.
扰乱昼夜节律与肥胖和癌症等代谢疾病有关.
生物钟维持新陈代谢平衡的精确机制尚未完全理解.

研究的目的:

研究昼夜时钟在调节脂肪细胞内的氧化代谢中的作用.
阐明昼夜干扰,线粒体功能和代谢功能障碍之间的联系.

主要方法:

在雄性小鼠中利用脂肪细胞特异性遗传删除来破坏昼夜时钟.
用高脂肪饮食来诱导代谢变化和昼夜干扰.
评估了脂肪细胞中的线粒体复合体I呼吸.
研究了对过氧体增殖器激活受体 (PPAR) 和胰岛素信号通路的影响.
使用酵母NDI1表达在脂肪细胞中恢复复合I功能.

主要成果:

脂肪细胞中循环时钟的破坏减少了线粒体复合体I呼吸.
这种减少导致PPAR和胰岛素信号通路的抑制.
通过NDI1的表达来恢复复合物I的功能,防止饮食和生理节律引起的代谢功能障碍,无论体重变化如何.

结论:

脂肪细胞的昼夜干扰会损害代谢健康,主要是通过线粒体复合体I功能障碍.
昼夜时钟对线粒体复合体I的调节是维持新陈代谢平衡的关键因素.
针对线粒体复合体I功能,为与昼夜干扰相关的代谢障碍提供了潜在的治疗策略.

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