Cell
Volume 171, Issue 2, 5 October 2017, Pages 372-384.e12
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Article
Adipose Tissue Macrophage-Derived Exosomal miRNAs Can Modulate In Vivo and In Vitro Insulin Sensitivity

https://doi.org/10.1016/j.cell.2017.08.035Get rights and content
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Highlights

  • Exosomes secreted by adipose tissue macrophages transfer miRNAs to insulin target cells

  • Treatment of lean mice with obese ATM exosomes causes insulin resistance

  • Treatment of obese mice with lean ATM exosomes improves insulin resistance

  • Obese ATM exosomes contain miR-155, which can cause insulin resistance

Summary

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

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

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