High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance.
Nat Commun
; 12(1): 213, 2021 01 11.
Article
em En
| MEDLINE
| ID: mdl-33431899
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilcolinas
/
Resistência à Insulina
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Regulação para Cima
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Exossomos
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Dieta Hiperlipídica
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article