"Micromanaging" metabolic syndrome

Metabolic diseases are characterized by the failure of regulatory genes or enzymes to effectively orchestrate specific pathways involved in the control of many biological processes. In addition to the classical regulators of metabolic homeostasis, recent discoveries have shown the remarkable role of small non-coding RNAs (microRNAs) in the post-transcriptional regulation of a number of genes, and their involvement in many pathological states, such as diabetes, atherosclerosis and cancer. Of note is microRNA-33 (miR-33), an intronic microRNA (miRNA) located within the sterol regulatory element-binding protein (SREBP) genes, one of the master regulators of cholesterol and fatty acid metabolism. We have recently shown that miR-33 regulates cholesterol efflux and high-density lipoprotein (HDL) formation, as well as fatty acid oxidation and insulin signaling. These results describe a model in which miR-33 works in concert with its host genes to ensure that the cell's metabolic state is balanced, thus highlighting the clinical potential of miRNAs as novel therapeutic targets for treating cardiometabolic diseases.