LAUSR

Obesity and nonalcoholic fatty liver disease (NAFLD) can reprogramme macrophages, leading to chronic inflammation and the development of nonalcoholic steatohepatitis (NASH). A study in Cell Reports investigated the role of an mRNAdestabilizing RNA modification, Nmethyladenosine (mA), in this process. Knockout (KO) of METTL3, an mA ‘writer’ protein, in myeloid lineage cells was protective against the development of inflammation and NAFLD symptoms in both aged mice and young mice fed a highfat diet (HFD). Expression of DDIT4, an mTORC1 inhibitor and regulator of ER stress, was upregulated in METTL3KO macrophages compared with wild-​type​macrophages​in vitro.​Increased​levels​of​DDIT4​ led to reduced NFκB signalling and reduced production of proinflammatory cytokines and markers of oxidative stress, lipogenesis and gluconeogenesis in METTL3KO mice fed a HFD. By contrast, knockdown of DDIT4 in METTL3KO macrophages abrogated these antiinflammatory effects. The authors conclude that mA modification of Ddit4 transcripts is important for macrophage reprogramming in obesity and NAFLD.