Sustained mitochondrial biogenesis is essential to maintain caloric restriction-induced beige adipocytes.
Sustained mitochondrial biogenesis is essential to maintain caloric restriction-induced beige adipocytes.
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DOI：
10.1016/j.metabol.2020.154225
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发表时间：
2020-04
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通讯作者：
Raja Gopal Reddy Mooli;D. Mukhi;M. Watt;L. Edmunds;Bingxian Xie;Joseph Capooci;Matthew C Reslink;Chetachukwu Eze;A. Mills;D. Stolz;M. Jurczak;S. Ramakrishnan
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文献类型：
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作者：
Raja Gopal Reddy Mooli;D. Mukhi;M. Watt;L. Edmunds;Bingxian Xie;Joseph Capooci;Matthew C Reslink;Chetachukwu Eze;A. Mills;D. Stolz;M. Jurczak;S. Ramakrishnan
背景限制热量摄入(CR)可延缓代谢和年龄相关疾病的发生。最近的研究表明，CR诱导的米色脂肪细胞的形成与脂肪组织的细胞外重塑、减轻脂肪组织的炎症反应和改善全身代谢稳态密切相关。6周龄C57BL6小鼠以40%CR饲料喂养6 周。随后，将其中一组小鼠的饮食改回青蛙饲料，再持续2 周。对脂肪组织进行组织学和生化检测。结果CR诱导的米色脂肪细胞在退出CR后迅速向白色脂肪细胞转化，而不依赖于parkin介导的有丝分裂。我们证明，在CR撤退过程中线粒体的退化与线粒体生物发生的减少密切相关。我们进一步证明，在β3-AR激动剂停用过程中，部分维持线粒体生物发生的CR可以减弱从米色到白色的脂肪转变。结论在CR模型中，我们的研究强调了线粒体生物发生在维持米色脂肪细胞中的主导作用。我们认为，CR可以减轻β3-AR激动剂停药引起的米色脂肪细胞的丢失。
BackgroundCaloric restriction (CR) delays the onset of metabolic and age-related disorders. Recent studies have demonstrated that formation of beige adipocytes induced by CR is strongly associated with extracellular remodeling in adipose tissue, decrease in adipose tissue inflammation, and improved systemic metabolic homeostasis. However, beige adipocytes rapidly transition to white upon CR withdrawal through unclear mechanisms.Materials and methodsSix-week old C57BL6 mice were fed with 40% CR chow diet for 6 weeks. Subsequently, one group of mice was switched back toad libitumchow diet, which was continued for additional 2 weeks. Adipose tissues were assessed histologically and biochemically for beige adipocytes.ResultsBeige adipocytes induced by CR rapidly transition to white adipocytes when CR is withdrawn independent of parkin-mediated mitophagy. We demonstrate that the involution of mitochondria during CR withdrawal is strongly linked with a decrease in mitochondrial biogenesis. We further demonstrate that beige-to-white fat transition upon β3-AR agonist-withdrawal could be attenuated by CR, partlyviamaintenance of mitochondrial biogenesis.ConclusionIn the model of CR, our study highlights the dominant role of mitochondrial biogenesis in the maintenance of beige adipocytes. We propose that loss of beige adipocytes upon β3-AR agonist withdrawal could be attenuated by CR.