MicroRNA-128 is involved in dexamethasone-induced lipid accumulation via repressing SIRT1 expression in cultured pig preadipocytes

Abstract In this study, pig preadipocytes were firstly treated with 10 −6 M DEX for 48 h to explore the role of dexamethasone (DEX, a chemically synthesized long-acting glucocorticoid) on lipid accumulation. Then, miRNA scrambled control (miR-SC), miR-128 overexpression plasmid and miR-128 inhibitor were respectively transfected into pig preadipocytes at 24 h before DEX treatment for 48 h (miR-SC-DEX, miR-128-DEX and miR-128-inhibitor-DEX) to illustrate the regulatory role of miR-128 on DEX-induced lipid accumulation. Compared with control preadipocytes, 10 -6 M Dex significantly increased triglyceride (TG) level, whereas the cell proliferation did not change. Moreover, 10 -6 M Dex obviously decreased sirtuin 1 (SIRT1) and its related lipolysis genes adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL) mRNA expression and enzyme activity, while significantly increased expression of adipogenesis genes peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α (C/EBP-α) and fatty acid synthase (FAS). In addition, 10 -6 M DEX significantly upregulated miR-128 expression, which was confirmed to directly target SIRT1 by bioinformatics analysis and dual-luciferase reporter assay. Gain- and loss-of-function study also showed that when compared with miR-SC-DEX cells, miR-128-DEX cells showed significantly reduced SIRT1 expression and increased TG level, as well as elevated cellular levels of PPAR-γ, C/EBP-α and FAS and suppressed ATGL and HSL expression and enzyme activity. In contrast, miR-128-inhibitor-DEX cells precisely presented the opposite results. Collectively, these results indicate that miR-128 plays a role in the pathogenesis of glucocorticoid-related abnormal lipid accumulation via repressing SIRT1 expression, consequently, miR-128 inhibition may represent a novel potential therapeutic target in preventing DEX-induced abnormal lipid accumulation.