MicroRNAs and lipid metabolism

Work over the past decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity, and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) metabolism. A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33. Work over the past 2 years has identified additional functions of miR-33 including the regulation of macrophage activation and mitochondrial metabolism. Moreover, it has recently been shown that miR-33 regulates vascular homeostasis and cardiac adaptation in response to pressure overload. In addition to miR-33 and miR-122, recent GWAS have identified single-nucleotide polymorphisms in the proximity of miRNA genes associated with abnormal levels of circulating lipids in humans. Several of these miRNAs, such as miR-148a and miR-128-1, target important proteins that regulate cellular cholesterol metabolism, including the LDL receptor (LDLR) and the ATP-binding cassette A1 (ABCA1). MicroRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for treating cardiometabolic disorders including atherosclerosis. Here, we discuss the recent findings in the field, highlighting the novel mechanisms by which miR-33 controls lipid metabolism and atherogenesis, and the identification of novel miRNAs that regulate LDL metabolism. Finally, we summarize the recent findings that identified miR-33 as an important noncoding RNA that controls cardiovascular homeostasis independent of its role in regulating lipid metabolism.