MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice.

Citation
Ying, W., et al. “Mir-690, An Exosomal-Derived Mirna From M2-Polarized Macrophages, Improves Insulin Sensitivity In Obese Mice.”. Cell Metabolism, pp. 781-790.e5.
Center UCSD-UCLA
Author Wei Ying, Hong Gao, Felipe Castellani Gomes Dos Reis, Gautam Bandyopadhyay, Jachelle M Ofrecio, Zhenlong Luo, Yudong Ji, Zhongmou Jin, Crystal Ly, Jerrold M Olefsky
Keywords exosomes, insulin sensitivity, macrophages, miR-690, obesity
Abstract

Insulin resistance is a major pathophysiologic defect in type 2 diabetes and obesity, while anti-inflammatory M2-like macrophages are important in maintaining normal metabolic homeostasis. Here, we show that M2 polarized bone marrow-derived macrophages (BMDMs) secrete miRNA-containing exosomes (Exos), which improve glucose tolerance and insulin sensitivity when given to obese mice. Depletion of their miRNA cargo blocks the ability of M2 BMDM Exos to enhance insulin sensitivity. We found that miR-690 is highly expressed in M2 BMDM Exos and functions as an insulin sensitizer both in vivo and in vitro. Expressing an miR-690 mimic in miRNA-depleted BMDMs generates Exos that recapitulate the effects of M2 BMDM Exos on metabolic phenotypes. Nadk is a bona fide target mRNA of miR-690, and Nadk plays a role in modulating macrophage inflammation and insulin signaling. Taken together, these data suggest miR-690 could be a new therapeutic insulin-sensitizing agent for metabolic disease.

Year of Publication
2021
Journal
Cell metabolism
Volume
33
Issue
4
Number of Pages
781-790.e5
Date Published
04/2021
ISSN Number
1932-7420
DOI
10.1016/j.cmet.2020.12.019
Alternate Journal
Cell Metab
PMID
33450179
PMCID
PMC8035248