GR-mediated FTO transactivation induces lipid accumulation in hepatocytes via demethylation of m⁶A on lipogenic mRNAs.

ABSTRACT: Chronic stress or excessive exposure to glucocorticoids (GC) contributes to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Glucocorticoid receptor (GR) mediates the action of GC, but its downstream signalling is not fully understood. Fat mass and obesity associated (FTO) protein and its demethylation substrate N6-methyladenosine (m⁶A) are both reported to participate in the regulation of lipid metabolism, yet it remains unknown whether they are involved in GC-induced hepatic lipid accumulation as new components of GR signalling. In this study, we use both in vivo and in vitro models of GC-induced hepatic lipid accumulation and demonstrate that the activation of lipogenic genes and accumulation of lipid in liver cells are mediated by GR-dependent FTO transactivati

SUBMITTER: Hu Y 

PROVIDER: S-EPMC7549648 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature