| Literature DB >> 33431899 |
Anil Kumar1, Kumaran Sundaram1, Jingyao Mu1, Gerald W Dryden1,2, Mukesh K Sriwastva1, Chao Lei1, Lifeng Zhang1, Xiaolan Qiu1, Fangyi Xu1, Jun Yan1, Xiang Zhang3, Juw Won Park4,5, Michael L Merchant6, Henry C L Bohler7, Baomei Wang8, Shuangqin Zhang9, Chao Qin10, Ziying Xu10, Xianlin Han10, Craig J McClain2, Yun Teng11, Huang-Ge Zhang12,13.
Abstract
High-fat diet (HFD) decreases insulin sensitivity. How high-fat diet causes insulin resistance is largely unknown. Here, we show that lean mice become insulin resistant after being administered exosomes isolated from the feces of obese mice fed a HFD or from patients with type II diabetes. HFD altered the lipid composition of exosomes from predominantly phosphatidylethanolamine (PE) in exosomes from lean animals (L-Exo) to phosphatidylcholine (PC) in exosomes from obese animals (H-Exo). Mechanistically, we show that intestinal H-Exo is taken up by macrophages and hepatocytes, leading to inhibition of the insulin signaling pathway. Moreover, exosome-derived PC binds to and activates AhR, leading to inhibition of the expression of genes essential for activation of the insulin signaling pathway, including IRS-2, and its downstream genes PI3K and Akt. Together, our results reveal HFD-induced exosomes as potential contributors to the development of insulin resistance. Intestinal exosomes thus have potential as broad therapeutic targets.Entities:
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Year: 2021 PMID： 33431899 PMCID： PMC7801461 DOI： 10.1038/s41467-020-20500-w
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919