Abstract

Lipid metabolism disorders and hepatic lipid deposition are major contributors to the development of metabolic diseases such as non-alcoholic fatty liver disease. Omega-3 fatty acids have been shown to exert beneficial effects on lipid homeostasis and liver function, but their molecular regulatory mechanisms remain incompletely understood. Here, we investigated the effects of omega-3 fatty acids on lipid metabolism and hepatic lipid deposition in addition to the modulatory role of miR-34a using an in vivo high-fat diet (HFD) model and an in vitro palmitic acid (PA)-induced HepG2 cell model. We assessed the effects of omega-3 fatty acid intervention and measured lipid levels in mouse serum, triglyceride (TG) and total cholesterol (TC) levels in the mouse liver, and TG levels in HepG2 cells. Further, we evaluated the mRNA and protein levels of miR-34a, SIRT1, SREBP-1c, CPT-1 A and PGC-1α. We observed that miR-34a expression was upregulated in the HFD and PA groups. Omega-3 fatty acid intervention reduced the serum levels of TG, TC, and low-density lipoproteins(LDL-C), and decreased the levels of TG and TC in the liver tissue, alleviating hepatocyte steatosis. Further, omega-3 fatty acids intervention reduced miR-34a and SREBP-1c expression, and increased the expression of SIRT1,PGC-1α, CPT-1 A. Moreover, miR-34a overexpression inhibited the effects of omega-3 fatty acids on SIRT1, SREBP-1c, PGC-1α and CPT-1 A. Thus, omega-3 fatty acids promote lipid metabolism, thereby reducing hepatic lipid deposition by down-regulating miR-34a expression.