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循环 microRNA-122 水平升高与年轻人肥胖和胰岛素抵抗有关。

Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults.

机构信息

Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors and E-Institutes of Shanghai Universities, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaLaboratory for Endocrine and MetabolismInstitute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors and E-Institutes of Shanghai Universities, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaLaboratory for Endocrine and MetabolismInstitute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors and E-Institutes of Shanghai Universities, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, ChinaLaboratory for Endocrine and MetabolismInstitute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Eur J Endocrinol. 2015 Mar;172(3):291-300. doi: 10.1530/EJE-14-0867. Epub 2014 Dec 16.

Abstract

OBJECTIVE

MicroRNAs (miRNAs) are involved in the regulation of adiposity, but functional studies have yielded inconclusive results. Examining the associations of circulating miRNAs levels with obesity and insulin sensitivity in humans may lead to improved insights.

DESIGN AND METHODS

Serum samples collected from 112 obese and control subjects (50.0% men) were randomly divided and combined into four pools (28 samples in each obese or control pool). The genome-wide circulating miRNA profiles were detected via microarray. Elevated miR-122 was selected and validated in individual serum samples from 123 obese (46.7% men) and 107 control (50.0% men) young adults. Associations between circulating miR-122 levels and parameters related to adiposity, insulin resistance, lipid profiles and hepatic enzymes were further assessed.

RESULTS

Thirty-four miRNAs were found to be expressed differently in the sera of obese patients compared with control subjects (P<0.001). Further analyses confirmed that obese patients had 3.07-fold higher circulating miR-122 levels than controls (P<0.001). Serum miR-122 levels were correlated with BMI (r=0.469), alanine aminotransferase (r=0.634), triglycerides (r=0.448), HDL-cholesterol (r=-0.351) and homeostasis model assessment of insulin resistance (r=0.401, all P<0.01). After controlling for confounding factors, miR-122 remained as an independent risk factor for insulin resistance (OR=3.379, 95% CI=1.141-10.007, P=0.028).

CONCLUSIONS

Elevated circulating miR-122 is positively associated with obesity and insulin resistance in young adults. These findings provide a better understanding regarding the role of miRNAs in adiposity and insulin sensitivity.

摘要

目的

微小 RNA(miRNAs)参与脂肪量的调节,但功能研究的结果尚无定论。检查循环 miRNA 水平与肥胖和人类胰岛素敏感性的关联可能会带来更好的认识。

设计和方法

从 112 名肥胖者和对照受试者(50.0%为男性)采集的血清样本被随机分为四组(每组肥胖组或对照组 28 个样本)。通过微阵列检测全基因组循环 miRNA 图谱。从 123 名肥胖(46.7%为男性)和 107 名对照(50.0%为男性)年轻成年人的个体血清样本中选择并验证了升高的 miR-122。进一步评估循环 miR-122 水平与肥胖相关参数、胰岛素抵抗、血脂谱和肝酶之间的关系。

结果

与对照组相比,肥胖患者血清中有 34 种 miRNA 的表达不同(P<0.001)。进一步分析证实,肥胖患者的循环 miR-122 水平比对照组高 3.07 倍(P<0.001)。血清 miR-122 水平与 BMI(r=0.469)、丙氨酸氨基转移酶(r=0.634)、甘油三酯(r=0.448)、高密度脂蛋白胆固醇(r=-0.351)和稳态模型评估的胰岛素抵抗(r=0.401,均 P<0.01)相关。在控制混杂因素后,miR-122 仍然是胰岛素抵抗的独立危险因素(OR=3.379,95%CI=1.141-10.007,P=0.028)。

结论

循环 miR-122 水平升高与年轻成年人肥胖和胰岛素抵抗呈正相关。这些发现提供了对 miRNA 在肥胖和胰岛素敏感性中的作用的更好理解。

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