MicroRNAs in metabolic disease

Abstract

Alterations in the metabolic control of lipid and glucose homeostasis predispose an individual to develop cardiometabolic diseases, such as type 2-diabetes mellitus and atherosclerosis. Work over the last years has suggested that microRNAs (miRNAs) play an important role in regulating these physiological processes. The contribution of miRNAs in regulating metabolism is exemplified by miR-33, an intronic miRNA encoded in the Srebp genes. miR-33 controls cellular cholesterol export and fatty acid degradation, whereas its host genes stimulate cholesterol and fatty acid synthesis. Other miRNAs, such as miR-122, also play a critical role in regulating lipid homeostasis by controlling cholesterol synthesis and lipoprotein secretion in the liver. This review article summarizes the recent findings in the field, highlighting the contribution of miRNAs in regulating lipid and glucose metabolism. We will also discuss how the modulation of specific miRNAs may be a promising strategy to treat metabolic diseases.

Figure 1. miRNA regulation of lipid metabolism, insulin signaling and glucose homeostasis

Schematic overview of miRNAs involved in the regulation of glucose and lipid metabolism. Red boxes highlight genes involved in lipid metabolism and blue boxes highlight those genes related to insulin signaling and glucose homeostasis. Unknown direct target genes or molecular mechanisms that regulate the highlighted genes are marked with a question mark. Note that the target genes showed in the figure are those validated experimentally but these genes can be also modulated by other miRNAs and the miRNAs highlighted can regulate other genes that do not appear in the figure.