Gonadal white adipose tissue-derived exosomal MiR-222 promotes obesity-associated insulin resistance

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 fro...

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Bibliographic Details
Published in:Aging (Albany, NY.) NY.), 2020-11, Vol.12 (22), p.22719-22743
Main Authors: Li, Dameng, Song, Huichen, Shuo, Linghu, Wang, Lei, Xie, Ping, Li, Weili, Liu, Jiachen, Tong, Yafei, Zhang, Chen-Yu, Jiang, Xiaohong, Li, Jing, Zhang, Yujing
Format: Article
Language:English
Subjects:
Adipose Tissue, White - metabolism
Animals
Diabetes Mellitus, Type 2 - blood
Female
Gonads - metabolism
HEK293 Cells
Humans
Insulin Resistance
Liver - metabolism
Male
Mice, Inbred C57BL
MicroRNAs - blood
Muscle, Skeletal - metabolism
Obesity - blood
Research Paper
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Summary: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.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.103891