Obesity-induced overexpression of miRNA-24 regulates cholesterol uptake and lipid metabolism by targeting SR-B1.

Scavenger Receptor B1 (SR-B1) is an 82 kDa integral membrane glycoprotein that mediates selective uptake of high-density lipoprotein cholesteryl ester (CE) in vitro and in vivo. Previously, we defined several kinds of regulatory mechanisms of SR-B1 expression and function. Here, we have dissected the function of a novel miR-24 on SR-B1 expression, HDL uptake and lipid metabolism. We showed that miR-24 was upregulated in HepG2 cells cultured in the mimicked hyperlipidemic condition and in the livers of dietary induced and genetic obesity mice. Overexpression of miR-24 inhibited SR-B1 expression by directly targeting SR-B1 3' UTR and repressed HDL uptake and steroidogenesis in steroidogenic cells. HepG2 cells with miR-24 showed attenuation of TG levels and lipid accumulation. Moreover, we validated that overexpression of miR-24 downregulated the expression of certain genes involved in lipogenesis, FASN, ACLY and SCD1, and increased the expression of genes of cholesterol synthesis, HMGCR, DHCR24 and SREBP2. Taken together, we demonstrated that obesity induced miR-24 repressed HDL uptake, steroid hormone synthesis and lipid metabolism by targeting SR-B1.