Blood microRNA profile associates with the levels of serum lipids and metabolites associated with glucose metabolism and insulin resistance and pinpoints pathways underlying metabolic syndrome: the cardiovascular risk in Young Finns Study

Abstract

Since metabolic syndrome (MetS) is a collection of cardiovascular risk factors involving multiple signaling systems, we related the metabolic abnormalities associated with MetS with circulating microRNA profiles to pinpoint the affected signaling pathways. The blood microRNA profile, genome wide gene expression and serum NMR metabolomics were analyzed from 71 participants of the Young Finns Study. We found nine microRNAs that associated significantly with metabolites connected to MetS. MicroRNA-144-5p concentration correlated with glucose levels, hsa-1207-5p with glycosylated hemoglobin and hsa-miR-484 with metabolites related to insulin resistance. Hsa-miR-625-3p correlated with cholesterol levels, hsa-miR-1237-3p and hsa-miR-331-3p expression with certain fatty acids levels and hsa-miR-129-1-3p, -129-2-3p, and -1288-3p with glycerol levels. The down-regulated targets of miR-1207-5p and -129-2-3p were enriched in PI3K and MAPK pathways and 8 out of the 12 enriched pathways were down-regulated in individuals with MetS. In conclusion microRNAs associated with several aspects of MetS, possibly regulating glucose and lipid metabolism.

Keywords: Diabetes; MRNA expression; Metabolic syndrome; MicroRNA; NMR metabolomics.