BACKGROUND Caloric 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 METHODS Six-week old C57BL6 mice were fed with 40% CR chow diet for 6 weeks. Subsequently, one group of mice was switched back to ad libitum chow diet, which was continued for additional 2 weeks. Adipose tissues were assessed histologically and biochemically for beige adipocytes. RESULTS Beige adipocytes induced by CR rapidly transition to white adipocytes when CR is withdrawn independent of parkin-mediated mitophagy.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, partly via maintenance of mitochondrial biogenesis. CONCLUSION In 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.

中文翻译：

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持续的线粒体生物发生对于维持热量限制诱导的米色脂肪细胞至关重要。

背景技术热量限制（CR）延迟了代谢和年龄相关疾病的发作。最近的研究表明，由CR诱导的米色脂肪细胞的形成与脂肪组织中的细胞外重塑，脂肪组织炎症的减少以及全身代谢稳态的改善密切相关。但是，米色脂肪细胞在CR撤回后通过不清楚的机制迅速转变为白色。材料与方法给六周大的C57BL6小鼠喂食40％CR饲料6周。随后，将一组小鼠改回随意饮食，继续饮食2周。组织学和生化评估脂肪组织的米色脂肪细胞。结果当CR撤回时，由CR诱导的米色脂肪细胞迅速转变为白色脂肪细胞，而与Parkin介导的细胞吞噬无关。我们证明CR撤回期间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，β3-AR激动剂退出后，米色至白色脂肪过渡可被CR减弱，部分是通过维持线粒体生物发生。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。我们建议CR可以减弱β3-AR激动剂撤药后米色脂肪细胞的丢失。我们进一步证明，β3-AR激动剂退出后，米色至白色脂肪过渡可被CR减弱，部分是通过维持线粒体生物发生。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。我们建议CR可以减弱β3-AR激动剂撤药后米色脂肪细胞的丢失。我们进一步证明，β3-AR激动剂退出后，米色至白色脂肪过渡可被CR减弱，部分是通过维持线粒体生物发生。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。我们建议CR可以减弱β3-AR激动剂撤药后米色脂肪细胞的丢失。