Background: Nonalcoholic fatty liver disease (NAFLD) represents the range from simple steatosis to severe steatohepatitis with inflammation and fibrosis. Dysregulated lipid metabolism and lipid deposition are well-known as early stages of NAFLD pathogenesis. Recently, we have found that miR-199a-3p and miR-126-3p are up-regulated in the liver tissue of NAFLD patients. Here we investigated the impact of the miRNAs in adipocyte differentiation and lipid metabolism-related gene expression.
Methods: Transfection of miRNAs into confluent mouse 3T3-L1 preadipocytes were performed by Lipofectamine RNAiMAX. After transfection, cells were differentiated by insulin, dexamethasone, 3-isobutyl-1-methylxanthine, and rosiglitazone for 3 days. Intracellular lipid deposition and mRNA expression were analyzed by Oil red O staining and quantitative RT-PCR, respectively.
Results: Both miR-199a-3p and miR-126-3p enhanced adipocyte differentiation compared to control miRNA. These miRNAs increased CCAAT/enhancer binding protein-α (C/EBPα) and decreased hypoxia-inducible factor (HIF)-1α expression.
Conclusion: It has been reported that HIF-1α reduces C/EBPα expression. Therefore, up-regulated miR-199a-3p and miR-126-3p might promote lipid deposition and adipocyte differentiation by targeting HIF-1α.