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雷帕霉素哺乳动物靶点信号通路调控小鼠棕色脂肪细胞的线粒体质量控制

Mammalian Target of Rapamycin Signaling Pathway Regulates Mitochondrial Quality Control of Brown Adipocytes in Mice.

作者信息

Huwatibieke Bahetiyaer, Yin Wenzhen, Liu Lingchao, Jin Yuxin, Xiang Xinxin, Han Jingyan, Zhang Weizhen, Li Yin

机构信息

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.

Department of Integration of Chinese and Western Medicine, Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.

出版信息

Front Physiol. 2021 Jul 14;12:638352. doi: 10.3389/fphys.2021.638352. eCollection 2021.

DOI:10.3389/fphys.2021.638352
PMID:34335285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8317026/
Abstract

The mammalian target of rapamycin (mTOR) is an important protein kinase that senses changes in extracellular and intracellular energy levels and plays a key role in regulating energy metabolism. Brown adipose tissue, which can be converted to white adipose tissue, contains a large number of mitochondria and regulates energy expenditure through thermogenesis. Because obesity is a process of fat accumulation due to chronic excessive energy intake, we attempted to determine whether the mTOR signaling pathway can affect the mitochondrial quality control of brown adipocytes through sensing energy status, thereby regulating brown/white adipocyte transformation. In the present study, through activation or inhibition of mTOR signaling, we detected mitochondrial biogenesis, dynamics, and autophagy-related markers in brown adipocytes. We found that activation of mTOR signaling downregulated the expression of mitochondrial biogenesis, dynamics, and autophagy-relevant markers and inhibited the mitochondrial quality control of brown adipocytes, indicating a phenotypic transformation of brown to white adipocytes. In contrast, inhibition of mTOR signaling upregulated the expression of mitochondrial biogenesis, dynamics, and mitophagy-relevant markers and strengthened mitochondrial quality control, suggesting an inhibition of the phenotypic transformation of brown to white adipocytes. In conclusion, the mTOR signaling pathway plays an important role in modulating the transformation of adipocytes by regulating mitochondrial quality control.

摘要

雷帕霉素靶蛋白(mTOR)是一种重要的蛋白激酶,可感知细胞外和细胞内能量水平的变化,并在调节能量代谢中起关键作用。可转化为白色脂肪组织的棕色脂肪组织含有大量线粒体,并通过产热调节能量消耗。由于肥胖是由于长期能量摄入过多导致的脂肪堆积过程,我们试图确定mTOR信号通路是否能通过感知能量状态影响棕色脂肪细胞的线粒体质量控制,从而调节棕色/白色脂肪细胞的转化。在本研究中,通过激活或抑制mTOR信号,我们检测了棕色脂肪细胞中线粒体生物发生、动力学和自噬相关标志物。我们发现,mTOR信号的激活下调了线粒体生物发生、动力学和自噬相关标志物的表达,并抑制了棕色脂肪细胞的线粒体质量控制,表明棕色脂肪细胞向白色脂肪细胞发生了表型转化。相反,抑制mTOR信号上调了线粒体生物发生、动力学和线粒体自噬相关标志物的表达,并加强了线粒体质量控制,提示抑制了棕色脂肪细胞向白色脂肪细胞的表型转化。总之,mTOR信号通路通过调节线粒体质量控制在调节脂肪细胞转化中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20d0/8317026/6d0f0ee01d2c/fphys-12-638352-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20d0/8317026/3c5ca7ec6a27/fphys-12-638352-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20d0/8317026/3c5ca7ec6a27/fphys-12-638352-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20d0/8317026/12f62d644191/fphys-12-638352-g002.jpg
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