Title: High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance.

Authors: Kumar, Anil; Sundaram, Kumaran; Mu, Jingyao; Dryden, Gerald W; Sriwastva, Mukesh K; Lei, Chao; Zhang, Lifeng; Qiu, Xiaolan; Xu, Fangyi; Yan, Jun; Zhang, Xiang; Park, Juw Won; Merchant, Michael L; Bohler, Henry C L; Wang, Baomei; Zhang, Shuangqin; Qin, Chao; Xu, Ziying; Han, Xianlin; McClain, Craig J; Teng, Yun; Zhang, Huang-Ge

Published In Nat Commun, (2021 01 11)

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.

PubMed ID: 33431899

MeSH Terms: No MeSH terms associated with this publication