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


ABSTRACT: 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.

SUBMITTER: Li D 

PROVIDER: S-EPMC7746358 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Li Dameng D   Song Huichen H   Shuo Linghu L   Wang Lei L   Xie Ping P   Li Weili W   Liu Jiachen J   Tong Yafei Y   Zhang Chen-Yu CY   Jiang Xiaohong X   Li Jing J   Zhang Yujing Y  

Aging 20201110 22


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  ...[more]

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