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miRNA Signatures of Insulin Resistance in Obesity
Author(s) -
Jones Angela,
Danielson Kirsty M.,
Benton Miles C.,
Ziegler Olivia,
Shah Ravi,
Stubbs Richard S.,
Das Saumya,
MacartneyCoxson Donia
Publication year - 2017
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.21950
Subject(s) - insulin resistance , obesity , microrna , medicine , endocrinology , phenotype , diabetes mellitus , insulin , biology , bioinformatics , gene , genetics
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 ( R 2 = 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.