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 m⁶A 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）经过快速的产后发育，然后可以防止感冒和肥胖，直至成年。然而，决定BAT的出生后发育和成熟的分子机制尚不清楚。在这里，我们显示METTL3（一种关键的RNA甲基转移酶）表达在出生后的肩s骨棕色脂肪组织（iBAT）中显着增加，并且在iBAT的出生后发展和成熟中起着至关重要的作用。BAT-特异性缺失的Mettl3 BAT的严重损害成熟体内通过降低米⁶的修饰和表达PRDM16，PPARG，和UCP1转录本，导致BAT介导的适应性生热作用显着减少，并促进高脂饮食（HFD）诱导的肥胖症和全身性胰岛素抵抗。这些数据表明METTL3是控制iBAT产后发育和能量稳态的重要调节剂。