MiRNA Signatures of Insulin Resistance in Obesity.

ABSTRACT:

Objective

Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity.

Methods

One hundred seventy-five miRNAs were analyzed in females with obesity (insulin sensitivity, n?=?11; insulin resistance, n?=?19; type 2 diabetes, n?=?15) and without obesity (n?=?12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated.

Results

One hundred six miRNAs were significantly (adjusted P???0.05) different between controls and at least one obesity phenotype, including miRNAs with the following attributes: previously reported roles in obesity and altered circulating levels (e.g., miR-122, miR-192); known roles in obesity but no reported changes in circulating levels (e.g., miR-378a); and no current reported role in, or association with, obesity (e.g., miR-28-5p, miR-374b, miR-32). The miRNAs in the latter group were found to be associated with extracellular vesicles. Forty-eight miRNAs showed significant correlations with clinical parameters; stepwise regression retained let-7b, miR-144-5p, miR-34a, and miR-532-5p in a model predictive of insulin resistance (R² ?=?0.57, P?=?7.5?×?10^-8 ). Both miR-378a and miR-122 were perturbed in metabolically relevant tissues in a murine model of obesity.

Conclusions

This study expands on the role of extracellular miRNAs in insulin-resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity.

SUBMITTER: Jones A 

PROVIDER: S-EPMC5614819 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature