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Cell. 2017 Oct 5;171(2):372-384.e12. doi: 10.1016/j.cell.2017.08.035. Epub 2017 Sep 21.

Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity.

Author information

1
Division of Endocrinology and Metabolism, Department of Medicine, UC San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
2
Pediatric Diabetes Research Center, Department of Pediatrics, UC San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
3
Center for Computational Biology and Bioinformatics, UC San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
4
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
5
Division of Endocrinology and Metabolism, Department of Medicine, UC San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: jolefsky@ucsd.edu.

Abstract

MiRNAs are regulatory molecules that can be packaged into exosomes and secreted from cells. Here, we show that adipose tissue macrophages (ATMs) in obese mice secrete miRNA-containing exosomes (Exos), which cause glucose intolerance and insulin resistance when administered to lean mice. Conversely, ATM Exos obtained from lean mice improve glucose tolerance and insulin sensitivity when administered to obese recipients. miR-155 is one of the miRNAs overexpressed in obese ATM Exos, and earlier studies have shown that PPARγ is a miR-155 target. Our results show that miR-155KO animals are insulin sensitive and glucose tolerant compared to controls. Furthermore, transplantation of WT bone marrow into miR-155KO mice mitigated this phenotype. Taken together, these studies show that ATMs secrete exosomes containing miRNA cargo. These miRNAs can be transferred to insulin target cell types through mechanisms of paracrine or endocrine regulation with robust effects on cellular insulin action, in vivo insulin sensitivity, and overall glucose homeostasis.

KEYWORDS:

PPARγ; adipose tissue macrophages; exosomes; glucose intolerance; insulin resistance; miR-155; miRNA; obesity

PMID:
28942920
DOI:
10.1016/j.cell.2017.08.035
[Indexed for MEDLINE]

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