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WTAP regulates postnatal development of brown adipose tissue by stabilizing METTL3 in mice

摘要Brown adipocyte maturation during postnatal development is essential for brown adipose tissue (BAT) to protect animals against cold. Impaired maturation of brown adipocytes leads to cold intolerance. However, the molecular mechanisms that determine the maturation of brown adipocytes during postnatal development are not fully understood. Here, we identify Wilms’ tumor 1-associating protein (WTAP) as an essential regulator in the postnatal development and maturation of BAT. BAT-specific knockout of Wtap (Wtap-BKO) severely impairs maturation of BAT in vivo by decreasing the expression of BAT-selective genes, leading to the whitening of interscapular BAT (iBAT). Single nucleus RNA-sequencing analysis shows the dynamic changes of cell heterogeneity in iBAT of Wtap-BKO mice. Adult mice with WTAP deficiency in BAT display hypothermic and succumb to acute cold challenge. Mechanistically, WTAP deficiency decreases m6A mRNA modification by reducing the protein stability of METTL3. BAT-specific overexpression of Mettl3 partially rescues the phenotypes observed in Wtap-BKO mice. These data demonstrate that WTAP/METTL3 plays an essential role in iBAT postnatal development and thermogenesis.

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作者 Yuqin Wang [1] Xinzhi Li [1] Cenxi Liu [2] Liying Zhou [3] Lei Shi [4] Zhiguo Zhang [4] Long Chen [1] Ming Gao [1] Lanyue Gao [5] Yuanyuan Xu [5] He Huang [3] Jin Li [2] Zheng Chen [1] 学术成果认领
作者单位 HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, China [1] School of Life Science, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200438, China [2] Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200438, China [3] Department of Cardiology, The First Hospital of Jilin University, Changchun, Jilin 130021, China [4] The Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, School of Public Health, China Medical University, Shenyang, Liaoning 110122, China [5]
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DOI 10.1093/lifemeta/loac028
发布时间 2024-07-26(万方平台首次上网日期,不代表论文的发表时间)
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