METTL3 is essential for postnatal development of brown adipose tissue and energy expenditure in mice

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.