Abstract
Non-alcoholic liver disease (NAFLD) is a condition caused by excessive fat accumulation in the liver and developed via multiple pathways. miR-27b has been suggested to play crucial roles in the development of NAFLD, assuming via targeting genes involved in lipid catabolism and anabolism. However, other pathways regulated by miR-27b are largely unknown. Here we show that lipid accumulation was induced in miR-27b-transfected human and mouse hepatic cells and that knockdowns of three miR-27b-target genes, β-1,4-galactosyltransferase 3 (B4GALT3), matrix AAA peptidase interacting protein 1 (MAIP1) and PH domain and leucine rich repeat protein phosphatase 2 (PHLPP2), induced lipid accumulation. We also show that B4GALT3 and MAIP1 were direct targets of miR-27b and overexpression of MAIP1 ameliorated miR-27b-induced lipid accumulation. In addition, we show that hepatic Maip1 expression declined in mice fed a high-fat diet, suggesting the involvement of decreased Maip1 expression in the condition of fatty liver. Overall, we identified MAIP1/miR-27b axis as a mediator of hepatic lipid accumulation, a potential therapeutic target for NAFLD.