Altered expression of miR-181a-5p and miR-23a-3p is associated with obesity and TNFα-induced insulin resistance.

Altered expression of miR-181a-5p and miR-23a-3p is associated with obesity and TNFα-induced insulin resistance.

J Clin Endocrinol Metab. 2018 Feb 01;:

Authors: Lozano-Bartolomé J, Llauradó G, Otin MP, Altuna-Coy A, Rojo-Martínez G, Vendrell J, Jorba R, Rodríguez-Gallego E, Chacón MR

Abstract
Context: The proinflammatory cytokine TNFα is a key player in insulin resistance (IR). While several miRNAs are believed to be involved in the development of adipose tissue (AT) IR, the role of miRNAs in the association between inflammation and IR is poorly understood.
Objective: To investigate the expression profile of miR-181a-5p and miR-23a-3p in obesity and to study their role in TNFα-induced IR in adipocytes.
Design: Two separate cohorts were employed. Cohort 1 was used for AT expression studies and included 28 subjects with BMI<30 and 30 subjects with BMI≥30. Cohort 2 was used for circulating serum miRNA studies and included 101 subjects with 4-years follow-up (48 cases and 53 controls). miR-181a-5p and miR-23a-3p expression was assessed in subcutaneous (SAT) and visceral (VAT) AT. Functional analysis was performed in adipocytes utilizing miRNA mimics and inhibitors. Key molecules of the insulin pathway, AKT, PTEN, AS160 and S6K, were analyzed.
Results: Expression of miR-181a-5p and miR-23a-3p was reduced in AT from obese and diabetic subjects and was inversely correlated to adiposity and HOMA-IR. 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 cases vs controls at baseline, pointing towards its prognostic value. Variable importance in projection scores revealed miR-181a-5p had more impact in the model than insulin or glucose at 120 minutes.
Conclusions: miR-181a-5p and miR-23a-3p may prevent TNFα-induced IR in adipocytes through modulation of PTEN and S6K expression.

PMID: 29409019 [PubMed - as supplied by publisher]

http://ift.tt/2C1uGYR