Mesencephalic astrocyte-derived neurotrophic factor alleviates alcohol induced hepatic steatosis via activating Stat3-mediated autophagy

Copyright © 2021 Elsevier Inc. All rights reserved..

Alcoholic fatty liver disease (AFLD) is induced by alcohol consumption and may progress to more severe liver diseases such as alcoholic steatohepatitis, fibrosis and cirrhosis, and even hepatocellular carcinoma. Mesencephalic astrocyte-derived neurotrophic factor (MANF) participates in maintaining lipid homeostasis. However, the role of MANF in the pathogenesis of AFLD remains unclear. We established an AFLD mouse model following the US National Institute on Alcohol Abuse and Alcoholism procedure. Both mRNA and protein levels of MANF were significantly increased in the chronic binge alcohol feeding model. Liver-specific knockout of MANF aggravated hepatic lipid accumulation. Similarly, liver-specific overexpression of MANF alleviated AFLD in mouse livers. MANF affected hepatic lipid metabolism by modulating autophagy. The levels of LC3-II and Atg5-Atg12 were decreased in mouse livers with MANF liver-specific knockout and increased with MANF liver-specific overexpression. Furthermore, MANF changed the phosphorylation of Stat3 and its nuclear localization. MANF may have a protective role in the development of AFLD.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:550

Enthalten in:

Biochemical and biophysical research communications - 550(2021) vom: 23. Apr., Seite 197-203

Sprache:

Englisch

Beteiligte Personen:

Zhang, Guorong [VerfasserIn]
Liu, Qinhui [VerfasserIn]
Li, Yanping [VerfasserIn]
Huang, Cuiyuan [VerfasserIn]
Zhou, Jian [VerfasserIn]
Zhao, Yingnan [VerfasserIn]
Wu, Tong [VerfasserIn]
Tang, Qin [VerfasserIn]
Li, Rui [VerfasserIn]
Zhang, Zijing [VerfasserIn]
Zhang, Jinhang [VerfasserIn]
Huang, Ya [VerfasserIn]
Huang, Hui [VerfasserIn]
Xia, Yan [VerfasserIn]
Yan, Jiamin [VerfasserIn]
Jing, Xiandan [VerfasserIn]
He, Jinhan [VerfasserIn]

Links:

Volltext

Themen:

3K9958V90M
Alcoholic fatty liver
Autophagy
Ethanol
Journal Article
MANF protein, mouse
Mesencephalic astrocyte-derived neurotrophic factor (MANF)
Nerve Growth Factors
Research Support, Non-U.S. Gov't
STAT3 Transcription Factor
Stat3
Stat3 protein, mouse

Anmerkungen:

Date Completed 22.06.2021

Date Revised 22.06.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.bbrc.2021.02.123

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM322706726