Jones Angela, Danielson Kirsty M, Benton Miles C, Ziegler Olivia, Shah Ravi, Stubbs Richard S, Das Saumya, Macartney-Coxson Donia
Biomarkers Group, Institute of Environmental Science and Research, Wellington, New Zealand.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Obesity (Silver Spring). 2017 Oct;25(10):1734-1744. doi: 10.1002/oby.21950. Epub 2017 Aug 21.
Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity.
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.
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 = 0.57, P = 7.5 × 10 ). Both miR-378a and miR-122 were perturbed in metabolically relevant tissues in a murine model of obesity.
This study expands on the role of extracellular miRNAs in insulin-resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity.
细胞外微小RNA（miRNA）是肥胖及相关疾病的功能性生物标志物；本研究调查了肥胖症胰岛素抵抗表型中的血浆miRNA。
分析了肥胖女性（胰岛素敏感，n = 11；胰岛素抵抗，n = 19；2型糖尿病，n = 15）和非肥胖女性（n = 12）的175种miRNA。研究了miRNA水平与临床参数之间的相关性以及小鼠肥胖模型中15种miRNA的水平。
106种miRNA在对照组与至少一种肥胖表型之间存在显著差异（校正P≤0.05），包括具有以下特征的miRNA：先前报道在肥胖中起作用且循环水平改变（例如，miR-122、miR-192）；在肥胖中起已知作用但未报道循环水平变化（例如，miR-378a）；目前未报道在肥胖中起作用或与肥胖相关（例如，miR-28-5p、miR-374b、miR-32）。发现后一组中的miRNA与细胞外囊泡相关。48种miRNA与临床参数显示出显著相关性；逐步回归在预测胰岛素抵抗的模型中保留了let-7b、miR-144-5p、miR-34a和miR-532-5p（R = 0.57，P = 7.5×10）。在肥胖小鼠模型中，miR-378a和miR-122在代谢相关组织中均受到干扰。
本研究扩展了细胞外miRNA在肥胖症胰岛素抵抗表型中的作用，并鉴定出先前与肥胖症无关的候选miRNA。
