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

miRNA Signatures of Insulin Resistance in Obesity.

Author information

1
Biomarkers Group, Institute of Environmental Science and Research, Wellington, New Zealand.
2
Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
3
Genomics Research Centre, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
4
The Wakefield Clinic, Wellington, New Zealand.

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.

PMID:
28834285
PMCID:
PMC5614819
DOI:
10.1002/oby.21950
[Indexed for MEDLINE]
Free PMC Article

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