miRNA Signatures of Insulin Resistance in Obesity.

miRNA Signatures of Insulin Resistance in Obesity.
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DOI:
10.1002/oby.21950
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发表时间:
2017-10
期刊:
Obesity (Silver Spring, Md.)
影响因子:
--
通讯作者:
Macartney-Coxson D
Macartney-Coxson D
中科院分区:
其他
文献类型:
--
作者:
Jones A;Danielson KM;Benton MC;Ziegler O;Shah R;Stubbs RS;Das S;Macartney-Coxson D

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细胞外microrna是肥胖和相关疾病的功能性生物标志物;我们研究了肥胖患者胰岛素抵抗表型中的血浆microrna。分析了175个microRNA,这些microRNA分别来自于患有(胰岛素敏感性n=11;胰岛素抵抗n=19; ii型糖尿病n=15)和非肥胖(n=12)的女性。研究了小鼠肥胖模型中15种microRNA水平与临床参数的相关性。106个microRNA在对照组和至少一种肥胖表型之间存在显著差异(调整后P≤0.05),包括先前报道在肥胖和循环水平改变中起作用的microRNA(例如miR-122, miR-192);已知在肥胖中起作用,但未报道其循环水平的变化(例如miR-378a);目前没有报道与肥胖相关的作用(如miR-28-5p, miR-374b, miR-32)。发现后一组的miRNA与细胞外囊泡有关。48个microRNA与临床参数有显著相关性;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 (R2 = 0.57, P=7.5 × 10-8)。在小鼠肥胖模型中,miR-378a和miR-122在代谢相关组织中受到干扰。本研究扩展了细胞外miRNA在肥胖胰岛素抵抗表型中的作用,并确定了以前与肥胖无关的候选miRNA。
Extracellular microRNAs represent functional biomarkers for obesity and related disorders; we investigated plasma microRNAs in insulin resistance phenotypes in obesity. 175 microRNA were analysed in females with (insulin sensitivity n=11; insulin resistance n=19; Type-II diabetes n=15) and without (n=12) obesity. Correlations between microRNA level and clinical parameters, and levels of 15 microRNA in a murine obesity model were investigated. 106 microRNA were significantly (adjusted P≤0.05) different between controls and at least one obesity phenotype, including microRNAs with: 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 level (e.g. miR-378a); no current reported role in, or association, with obesity (e.g. miR-28-5p, miR-374b, miR-32). miRNA in the latter group were found to be associated with extracellular vesicles. 48 microRNA 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). 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 miRNA in insulin resistant phenotypes of obesity and identifies candidate miRNA not previously associated with obesity.
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