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

Biochem Biophys Res Commun. 2021 Apr 23:550:197-203. doi: 10.1016/j.bbrc.2021.02.123. Epub 2021 Mar 10.

Abstract

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.

Keywords: Alcoholic fatty liver; Autophagy; Mesencephalic astrocyte-derived neurotrophic factor (MANF); Stat3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy* / drug effects
  • Binge Drinking
  • Ethanol / pharmacology
  • Fatty Liver, Alcoholic / metabolism*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Growth Factors / deficiency
  • Nerve Growth Factors / metabolism*
  • Phosphorylation
  • STAT3 Transcription Factor / metabolism*

Substances

  • MANF protein, mouse
  • Nerve Growth Factors
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Ethanol