REPTOR和CREBRF编码了肌肉能量代谢的关键调节剂
Pedro Saavedra1, Phillip A Dumesic2,3, Yanhui Hu4
1Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA. psaavedra@hms.harvard.edu.
Nature communications
|August 15, 2023
概括
肌肉组织的代谢灵活性对健康至关重要. 这项研究揭示了REPTOR (及其哺乳动物对应物CREBRF) 作为肌肉能量代谢的关键调节者,影响糖解和氧化途径.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 代谢调节 代谢调节 代谢调节
- 肌肉生理学 肌肉生理学
背景情况:
- 肌肉中的代谢灵活性对于调整基质利用和保持代谢健康至关重要.
- 肌肉代谢灵活性的破坏与代谢疾病的发展有关.
- 系统代谢功能障碍会影响肌肉能量恒温.
研究的目的:
- 研究转录因子REPTOR在调节肌肉能量代谢中的作用.
- 探索REPTOR在Drosophila系统代谢功能障碍模型中的功能.
- 确定REPTOR及其哺乳动物正方体CREBRF在肌肉代谢中的保存功能.
主要方法:
- 利用Drosophila melanogaster模型与Yorkie诱导的肠道瘤来研究系统代谢功能障碍.
- 研究了在代谢压力下成年的肌肉中的REPTOR激活.
- 在Drosophila进行了体内研究,以评估REPTOR活性对葡萄糖代谢和TCA循环的影响.
- 研究了CREBRF在小鼠髓管中的功能,以评估其对糖解和氧化代谢的影响.
主要成果:
- REPTOR在肠道瘤的的肌肉中被激活,调节葡萄糖代谢.
- 野生型肌肉中持续的REPTOR活性抑制糖解并提高三碳酸 (TCA) 循环代谢产物.
- 在小鼠肌管中增加的CREBRF水平会降低糖解并增强氧化代谢.
- 确定了REPTOR和CREBRF在调节肌肉基质利用中的保留作用.
结论:
- REPTOR是肌肉能量代谢,特别是葡萄糖利用的关键调节器.
- CREBRF是REPTOR的哺乳动物正体,在调节肌肉糖解和氧化代谢方面具有相同的功能.
- 这些发现强调了REPTOR/CREBRF作为与肌肉代谢受损相关的代谢疾病的潜在治疗点.
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