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. 2017 Oct;25(10):1734-1744.
doi: 10.1002/oby.21950. Epub 2017 Aug 21.

miRNA Signatures of Insulin Resistance in Obesity

Angela Jones  1 , Kirsty M Danielson  2 , Miles C Benton  1   3 , Olivia Ziegler  2 , Ravi Shah  2 , Richard S Stubbs  4 , Saumya Das  2 , Donia Macartney-Coxson  1
Affiliations

miRNA Signatures of Insulin Resistance in Obesity

Angela Jones et al. Obesity (Silver Spring). 2017 Oct.

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.

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Conflict of interest statement

Disclosure: The authors have nothing to disclose and declare no conflict of interest

Figures

Figure 1
Figure 1. Levels of 15 plasma miRNA in a mouse model of obesity, fold change relative to controls
Fold change was calculated using the formula 2-ΔΔCt. * indicates significance at P<≤0.05 (two-tailed) and + at P≤ 0.05 (one-tailed).
Figure 2
Figure 2
Tissue miRNA expression levels in a mouse model of obesity, fold change relative to controls. Levels of miR-192, miR-122, miR-378a, let-7d, let-7e and let-7f in heart (H), liver (L), pericardial adipose (PF), subcutaneous adipose (SC) and visceral adipose (VF). * indicates significance at P<≤0.05 (two-tailed) and + at P≤ 0.05 (one-tailed). Fold change was calculated using the formula 2-ΔΔCt
See this image and copyright information in PMC

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