In mouse models, Zou et al. demonstrated that lncRNA MEG3 (maternally expressed gene 3) upregulates the sirtuin 6 (SIRT6) and enhancer of zeste homolog 2 (EZH2) genes, which regulate fat accumulation, inflammation, and the development of NAFLD. Here, SIRT6 is linked to metabolic dysfunction-associated steatotic liver disease.