HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China.
Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), School of Life Sciences, Northeast Normal University, Changchun, 130024, China.
Nat Commun. 2020 Apr 3;11(1):1648. doi: 10.1038/s41467-020-15488-2.
Brown adipose tissue (BAT) undergoes rapid postnatal development and then protects against cold and obesity into adulthood. However, the molecular mechanism that determines postnatal development and maturation of BAT is largely unknown. Here we show that METTL3 (a key RNA methyltransferase) expression increases significantly in interscapular brown adipose tissue (iBAT) after birth and plays an essential role in the postnatal development and maturation of iBAT. BAT-specific deletion of Mettl3 severely impairs maturation of BAT in vivo by decreasing mA modification and expression of Prdm16, Pparg, and Ucp1 transcripts, which leads to a marked reduction in BAT-mediated adaptive thermogenesis and promotes high-fat diet (HFD)-induced obesity and systemic insulin resistance. These data demonstrate that METTL3 is an essential regulator that controls iBAT postnatal development and energy homeostasis.
棕色脂肪组织（BAT）在出生后迅速发育，然后在成年期抵御寒冷和肥胖。然而，决定 BAT 出生后发育和成熟的分子机制在很大程度上是未知的。在这里，我们表明 METTL3（一种关键的 RNA 甲基转移酶）的表达在出生后显著增加，在肩胛间棕色脂肪组织（iBAT）的出生后发育和成熟中起着重要作用。BAT 特异性敲除 Mettl3 会严重损害 BAT 的成熟，方法是减少 mA 修饰和 Prdm16、Pparg 和 Ucp1 转录本的表达，这导致 BAT 介导的适应性产热显著减少，并促进高脂肪饮食（HFD）诱导的肥胖和全身胰岛素抵抗。这些数据表明，METTL3 是一种必不可少的调节剂，可控制 iBAT 的出生后发育和能量稳态。
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