脂肪组织中BCAA代谢受损促进了与年龄相关的代谢障碍
Hye-Sook Han1, Eunyong Ahn2, Eun Seo Park3
1Division of Life Sciences, Korea University, Seoul, Korea.
Nature aging
|July 24, 2023
概括
脂肪组织分支链氨基酸 (BCAA) 代谢障碍导致与年龄相关的代谢下降. 通过Crtc2淘汰恢复脂肪细胞中的BCAA分解,可以逆转这种衰老效应.
科学领域:
- 代谢的恒常状态 (metabolic homeostasis) 是指代谢过程中的恒常状态.
- 脂肪组织生物学 脂肪组织生物学
- 衰老研究研究 衰老研究
背景情况:
- 脂肪组织功能障碍有助于与年龄有关的代谢障碍.
- 成熟脂肪细胞在衰老中的具体作用尚不清楚.
- 分支链氨基酸 (BCAA) 代谢对代谢健康至关重要.
研究的目的:
- 为了研究脂肪组织BCAA代谢在衰老中的作用.
- 为了确定脂肪细胞特异性Crtc2淘汰对代谢衰老的影响.
- 阐明BCAA代谢,mTORC1信号传递和脂肪组织衰老中的细胞衰老之间的机制.
主要方法:
- 脂肪细胞特定的Crtc2淘汰赛小鼠模型.
- 多组学分析 (包括转录组学和代谢组学).
- 脂肪组织的单细胞RNA测序 (scRNA-seq).
- 评估细胞衰老和脂肪生成潜力.
主要成果:
- 脂肪细胞特异性Crtc2淘汰保护小鼠免受与年龄相关的代谢衰退.
- 在老化的内脏脂肪组织中观察到受损的BCAA代谢和激活的mTORC1信号.
- Crtc2 淘汰恢复了 BCAA 代谢,减少了 mTORC1 信号传递,并缓解了细胞衰老.
- 通过调节与衰老相关的BCAA-mTORC1分泌表型轴,Crtc2淘汰赛恢复了老化的内脏脂肪组织的脂肪生成潜力.
结论:
- 通过CRTC2扰乱BCAA代谢是与年龄相关的脂肪组织重塑的关键驱动因素.
- 脂肪细胞中的CRTC2在衰老过程中极大地影响代谢平衡.
- 准脂肪组织中的BCAA代谢可能为与年龄相关的代谢障碍提供治疗策略.
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