Nature子刊：高脂饮食通过外泌体促进胰岛素抵抗 | 热心肠日报
High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance
高脂饮食诱导的外泌体磷脂酰胆碱上调有助于胰岛素抵抗
10.1038/s41467-020-20500-w
01-11, Article
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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.
First Authors:
Anil Kumar
Correspondence Authors:
Yun Teng,Huang-Ge Zhang
All Authors:
Anil Kumar,Kumaran Sundaram,Jingyao Mu,Gerald W Dryden,Mukesh K Sriwastva,Chao Lei,Lifeng Zhang,Xiaolan Qiu,Fangyi Xu,Jun Yan,Xiang Zhang,Juw Won Park,Michael L Merchant,Henry C L Bohler,Baomei Wang,Shuangqin Zhang,Chao Qin,Ziying Xu,Xianlin Han,Craig J McClain,Yun Teng,Huang-Ge Zhang