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

• Published in: Aging (Albany, NY.) Vol. 12; no. 22; pp. 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: Journal Article
• Language: English
• Published: United States Impact Journals 10-11-2020
• 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; adipose; skeletal muscle; liver; insulin resistance; miR-222
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.103891

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.