Abstract
PURPOSE: MicroRNA (miRNA) profiling of visceral adipose tissue in Type-2 diabetes mellitus (T2DM) remains limited. We compared the expression of obesity-associated miRNAs in visceral fat from individuals with T2DM versus metabolically healthy obesity (MHO) and examined Raf kinase inhibitory protein (RKIP) as a candidate miR-543 target. METHODS: Visceral fat biopsies were obtained from adults with T2DM (n = 8) and MHO (n = 11). Thirteen miRNAs previously linked to obesity were quantified, and RKIP expression was evaluated at the mRNA level and by immunohistochemistry, including phosphorylated RKIP (pRKIP). RESULTS: Of the 13 miRNAs analyzed, miR-23a-3p and miR-543 were upregulated in T2DM (p = 0.032 and p = 0.009, respectively), whereas miR-320a-3p was downregulated (p = 0.009). RKIP mRNA levels did not differ between groups; however, in MHO adipocytes, RKIP mRNA correlated positively with miR-543 expression (r = 0.655, p = 0.034). Total RKIP protein was comparable between groups, while pRKIP was significantly higher in T2DM adipocytes (p = 0.012). CONCLUSIONS: Posttranscriptional regulation in visceral adipocytes differs between T2DM and MHO. Increased miR-543 and elevated pRKIP in T2DM suggest a rapid shift in regulatory signaling consistent with enhanced lipolysis and a proinflammatory milieu. Further studies are warranted to delineate the pRKIP-associated pathways in adipose tissue remodeling in T2DM.