Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Chongqing Key Laboratory of Precision Optics, Chongqing Institute of East China Normal University, Chongqing, 401120, China.
Adv Sci (Weinh). 2023 Sep;10(25):e2300436. doi: 10.1002/advs.202300436. Epub 2023 Jul 5.
N6-methyladenosine (m A) modification has been implicated in the progression of obesity and metabolic diseases. However, its impact on beige fat biology is not well understood. Here, via m A-sequencing and RNA-sequencing, this work reports that upon beige adipocytes activation, glycolytic genes undergo major events of m A modification and transcriptional activation. Genetic ablation of m A writer Mettl3 in fat tissues reveals that Mettl3 deficiency in mature beige adipocytes leads to suppressed glycolytic capability and thermogenesis, as well as reduced preadipocytes proliferation via glycolytic product lactate. In addition, specific modulation of Mettl3 in beige fat via AAV delivery demonstrates consistently Mettl3's role in glucose metabolism, thermogenesis, and beige fat hyperplasia. Mechanistically, Mettl3 and m A reader Igf2bp2 control mRNA stability of key glycolytic genes in beige adipocytes. Overall, these findings highlight the significance of m A on fat biology and systemic energy homeostasis.
N6-甲基腺苷（m6A）修饰与肥胖和代谢性疾病的进展有关。然而，其对米色脂肪生物学的影响尚不清楚。通过 m6A 测序和 RNA 测序，本研究报告称，在米色脂肪细胞激活时，糖酵解基因经历了 m6A 修饰和转录激活的重大事件。脂肪组织中 m6A 写入器 Mettl3 的基因缺失表明，成熟米色脂肪细胞中 Mettl3 的缺乏导致糖酵解能力和产热能力受到抑制，以及通过糖酵解产物乳酸减少前脂肪细胞增殖。此外，通过 AAV 传递在米色脂肪中特异性调节 Mettl3 一致表明 Mettl3 在葡萄糖代谢、产热和米色脂肪增生中的作用。在机制上，Mettl3 和 m6A 阅读器 Igf2bp2 控制米色脂肪细胞中关键糖酵解基因的 mRNA 稳定性。总的来说，这些发现强调了 m6A 在脂肪生物学和全身能量平衡中的重要性。
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