在编排棕色和白色脂肪细胞转录组和系统代谢方面,m6A的不同作用
Ling Xiao1, Dario F De Jesus1, Cheng-Wei Ju2
1Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center; Department of Medicine, BIDMC; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
Nature communications
|January 9, 2025
概括
由METTL14规范的N6-甲基氨酸 (m6A) 修饰在棕色和白色脂肪中具有不同的作用. METTL14通过控制脂肪细胞命运和代谢途径,影响胰岛素敏感性.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 代谢过程中的代谢.
背景情况:
- N6-甲基氨酸 (m6A) 是一种流行的mRNA修饰,但其组织特异性功能尚未完全理解.
- METTL14是m6A甲基化中的关键酶,其作用在脂肪组织亚型中需要阐明.
研究的目的:
- 研究METTL14在棕色脂肪组织 (BAT) 和白色脂肪组织 (WAT) 中细胞类型特定的调节作用.
- 确定METTL14对不同脂肪储存中的代谢结果和胰岛素敏感性的影响.
主要方法:
- 对人类和具有胰岛素抵抗性的小鼠在BAT和WAT中的METTL14表达的比较分析.
- 在BAT和WAT中生成和分析Mettl14-knockout模型.
- 整合m6A-seq和RNA-seq以确定差异调节的途径.
- 在稳定的METTL14-knockout人类棕色和白色脂肪细胞 (hBAs/hWAs) 中的验证.
主要成果:
- 在BAT和WAT中,METTL14表达与胰岛素敏感性相关.
- 在BAT中Mettl14-knockout通过前列腺素分泌增强胰岛素敏感性.
- 在WAT中Mettl14-Knockout诱导脂肪细胞亡和胰岛素抵抗.
- 在BAT中,METTL14缺陷对前列腺素生物合成和在WAT中对亡途径进行上调,影响特定的mRNA标.
结论:
- METTL14对脂肪组织代谢和胰岛素敏感性进行细胞类型特定的控制.
- 通过METTL14的m6A修饰会影响脂肪细胞的命运和全身代谢健康.
- 针对METTL14介导的m6A通路可能为代谢疾病提供治疗策略.
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