在BAT热生成中的性别差异取决于小鼠的PGC-1α介导的脂合成
Akira Takeuchi1, Kazutaka Tsujimoto2, Jun Aoki1
1Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Nature communications
|July 14, 2025
概括
过氧体增殖器激活受体马协作激活剂1-α (PGC-1α) 驱动棕色脂肪组织 (BAT) 在雌性小鼠中的热生成. PGC-1α调节脂合成和雌激素信号,影响能量消耗.
科学领域:
- 代谢过程中的代谢.
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
背景情况:
- 棕色脂肪组织 (BAT) 对能量消耗至关重要,并表现出基于性别的功能差异.
- 雌性小鼠显示出比雄性更高的BAT热生成活性,但潜在的分子机制仍然不清楚.
研究的目的:
- 阐明PGC-1α在BAT的性别特异性热生成功能的作用和机制.
- 调查PGC-1α,Chrebpβ,雌激素信号传递和女性脂质生成之间的相互作用.
主要方法:
- 使用诱导性脂肪细胞特异性PGC-1α淘汰 (KO) 鼠标模型.
- 对碳水化合物反应元素结合蛋白β (Chrebpβ) 进行了BAT特定的淘汰.
- 采用了脂组学和基因表达分析.
主要成果:
- 雌性小鼠的PGC-1α缺乏导致线粒体缺陷,并减少了BAT热生成.
- 在雌性KO小鼠中观察到Chrebpβ和de novo脂质生成 (DNL) 相关基因的减少表达.
- PGC-1α调节以太结合的甲基乙醇胺和心脏脂蛋白水平,并增强雌激素信号传导灵敏度.
结论:
- PGC-1α在通过脂合成调节BAT热生成方面发挥着关键的性别依赖作用.
- PGC-1α-Chrebpβ轴和雌激素信号是女性BAT功能和能量消耗的关键决定因素.
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