Apolipoprotein A-I improves hepatic autophagy through the AMPK pathway.
Biochimie
; 165: 210-218, 2019 Oct.
Article
en En
| MEDLINE
| ID: mdl-31401190
ABSTRACT
Dysfunction in lipid metabolism may result in a decrease in hepatic autophagy, which contributes to the pathogenesis of non-alcoholic steatohepatitis. ATP-binding cassette transporter A1 transports free cholesterol and phospholipids to apolipoprotein A-I (apoA-I) to form nascent high-density lipoprotein particles. Results from previous studies showed that the overexpression of apoA-I significantly reduced levels of hepatic lipids and endoplasmic reticulum stress by modifying lipid transport. Here, we investigated the effects of apoA-I overexpression on hepatic autophagy in cultured hepatocytes and mice. The overexpression of apoA-I in HepG2 cells resulted in an increase in the levels of autophagy as well as the phosphorylation of AMP-activated protein kinase α (AMPKα) and ULK1 and a decrease in the phosphorylation of mammalian target of rapamycin (mTOR). An AMPK inhibitor and siRNA eliminated this apoA-I effect. Consistently, apoA-I transgenic mice showed increased autophagy and AMPKα phosphorylation. These results suggest that apoA-I overexpression alleviates steatohepatitis by increasing hepatic autophagy through the AMPK-mTOR-ULK1 pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apolipoproteína A-I
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Hepatocitos
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Péptidos y Proteínas de Señalización Intracelular
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Proteínas Quinasas Activadas por AMP
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Hígado Graso
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Serina-Treonina Quinasas TOR
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Homólogo de la Proteína 1 Relacionada con la Autofagia
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Hígado
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochimie
Año:
2019
Tipo del documento:
Article
País de afiliación:
China