Excessive
lipid deposition is a hallmark of
NAFLD. Although much has been learned about the
enzymes and metabolites involved in
NAFLD, few studies have focused on the role of long noncoding RNAs (lncRNAs) in hepatic
lipid accumulation. Here, using in vitro and in vivo models of
NAFLD, we found that the
lncRNA Gm15622 is highly expressed in the liver of obese mice fed a HFD and in murine liver (AML-12) cells treated with
free fatty acids. Investigating the molecular mechanism in the liver-enriched expression of Gm15622 and its effects on
lipid accumulation in hepatocytes and on
NAFLD pathogenesis, we found that Gm15622 acts as a sponge for the
microRNA miR-742-3p. This sponging activity increased the expression of the transcriptional regulator
SREBP-1c and promoted
lipid accumulation in the liver of the HFD mice and AML-12 cells. Moreover, further results indicated that
metformin suppresses Gm15622 and alleviates
NAFLD-associated
lipid deposition in mice. In conclusion, we have identified an
lncRNA Gm15622/miR-742-3p/
SREBP-1c regulatory circuit associated with
NAFLD in mice, a finding that significantly advances our insight into how lipid metabolism and accumulation are altered in this metabolic disorder. Our results also suggest that Gm15622 may be a potential therapeutic target for managing
NAFLD.