Gonadal white adipose tissue-derived exosomal MiR-222 promotes obesity-associated insulin resistance.
Gonadal white adipose tissue-derived exosomal MiR-222 promotes obesity-associated insulin resistance.
复制标题
性腺白色脂肪组织来源的外泌体 MiR-222 促进肥胖相关的胰岛素抵抗
DOI：
10.18632/aging.103891
复制
发表时间：
2020-11-10
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li D;Song H;Shuo L;Wang L;Xie P;Li W;Liu J;Tong Y;Zhang CY;Jiang X;Li J;Zhang Y
在这项研究中，我们研究了血清外泌体miR-222在肥胖相关胰岛素抵抗中的作用。生物信息学分析显示，miR-222水平在具有胰岛素抵抗的肥胖患者的白色脂肪组织（GSE 25402数据集）和来自2型糖尿病（T2 DM）患者的血清样品（GSE 90028数据集）中显著上调。此外，在脂肪组织特异性Dicer基因敲除小鼠（GitHub数据集）和糖尿病模型小鼠（GSE 81976和GSE 85101数据集）中分析miRNA表达，性腺白色脂肪组织（gWAT）是血清外泌体miR-222的主要来源。miR-222水平在高脂饮食（HFD）小鼠的血清、血清外泌体和gWAT中显著升高，并且在其肝脏和骨骼肌组织中存在IRS 1和磷酸化AKT水平的相应下调，这与胰岛素敏感性受损和葡萄糖耐受不良相关。通过手术从HFD喂养的小鼠中移除gWAT来消除这些作用。因此，gWAT衍生的血清外泌体miR-222似乎通过抑制IRS 1表达来促进HFD喂养的肥胖小鼠的肝脏和骨骼肌中的胰岛素抵抗。
In this study, we investigated the role of serum exosomal miR-222 in obesity-related insulin resistance. Bioinformatics analyses showed that miR-222 levels were significantly upregulated in the white adipose tissue of obese patients with insulin resistance (GSE25402 dataset) and in serum samples from type 2 diabetes mellitus (T2DM) patients (GSE90028 dataset). Moreover, analysis of miRNA expression in adipose tissue-specific Dicer knockout mice (GitHub dataset) and diabetic model mice (GSE81976 and GSE85101 datasets), gonadal white adipose tissue (gWAT) was the main source of serum exosomal miR-222. MiR-222 levels were significantly elevated in the serum, serum exosomes and gWAT of mice fed a high-fat diet (HFD), and there was a corresponding downregulation of IRS1 and phospho-AKT levels in their liver and skeletal muscle tissues, which correlated with impaired insulin sensitivity and glucose intolerance. These effects were abrogated by surgically removing the gWAT from the HFD-fed mice. Thus, gWAT-derived serum exosomal miR-222 appears to promote insulin resistance in the liver and skeletal muscle of HFD-fed obese mice by suppressing IRS1 expression.
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DOI：
10.1073/pnas.1808855115
发表时间：
2018-11-27
影响因子：
11.1
作者：
Castano, Carlos;Kalko, Susana;Parrizas, Marcelina
通讯作者：
Parrizas, Marcelina
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB
影响因子：
4.4
作者：
Guduric-Fuchs J;O'Connor A;Camp B;O'Neill CL;Medina RJ;Simpson DA
通讯作者：
Simpson DA
影响因子：
8.2
作者：
Herrera, B. M.;Lockstone, H. E.;Taylor, J. M.;Ria, M.;Barrett, A.;Collins, S.;Kaisaki, P.;Argoud, K.;Fernandez, C.;Travers, M. E.;Grew, J. P.;Randall, J. C.;Gloyn, A. L.;Gauguier, D.;McCarthy, M. I.;Lindgren, C. M.
通讯作者：
Lindgren, C. M.
影响因子：
--
作者：
Jura, Magdalena;Kozak, Leslie. P.
通讯作者：
Kozak, Leslie. P.