High fat diet mice intestinal epithelial exosomal proteins were analyzed by MSMS.

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 high-fat diet (HFD) or from human type II diabetic patients with diabetes. HFD altered the lipid composition of exosomes from predominantly PE in exosomes from lean animals (L-Exo) to 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.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Intestinal Epithelial Cell

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: Anil Kumar  

LAB HEAD: Huang-Ge Zhang

PROVIDER: PXD022641 | Pride | 2021-03-23

REPOSITORIES: Pride