Altered Expression of miR-181a-5p and miR-23a-3p Is Associated With Obesity and TNFα-Induced Insulin Resistance.

Abstract

The proinflammatory cytokine TNFα is a key player in insulin resistance (IR). The role of miRNAs in inflammation associated with IR is poorly understood. To investigate miR-181a-5p and miR-23a-3p expression profiles in obesity and to study their role in TNFα-induced IR in adipocytes. Two separate cohorts were used. Cohort 1 was used in adipose tissue (AT) expression studies and included 28 subjects with body mass index (BMI) Expression of miR-181a-5p and miR-23a-3p was reduced in adipose tissue from obese and diabetic subjects and was inversely correlated to adiposity and homeostasis model assessment of IR index. Overexpression of miR-181a-5p and miR-23a-3p in adipocytes upregulated insulin-stimulated AKT activation and reduced TNFα-induced IR, regulating PTEN and S6K expression. Serum levels of miR-181a-5p were reduced in case vs control subjects at baseline, suggesting a prognostic value. Variable importance in projection scores revealed miR-181a-5p had more effect on the model than insulin or glucose at 120 minutes. miR-181a-5p and miR-23a-3p may prevent TNFα-induced IR in adipocytes through modulation of PTEN and S6K expression.