The inhibitory effect of ethanol on Sestrin3 in the pathogenesis of ethanol-induced liver injury

Xinqin Kang, Kateryna Petyaykina, Rongya Tao, Xiwen Xiong, X. Dong, Suthat Liangpunsakul

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Sestrins (Sesns) are a family of stress-sensitive genes that have been suggested to regulate lipid metabolism. Chronic ethanol feeding is known to cause lipid accumulation in hepatocytes. This study was designed to investigate the role of Sesn3 in the pathogenesis of alcohol-induced hepatic steatosis. We demonstrated that ethanol inhibited the expression of Sesn3 in VL-17A cells. Overexpression of Sesn3 ameliorated triglyceride accumulation; downregulation using short hairpin RNA significantly deteriorated triglyceride accumulation in these cells. The expression of Sesn3 was also reduced in mice fed with ethanol for 4 wk. Overexpression of Sesn3 prevented hepatic steatosis, whereas knockdown of Sesn3 worsened hepatic steatosis in ethanol-fed mice. Overexpression of Sesn3 significantly reduced the expression of genes encoding for lipid synthesis through AMPK pathway. Overexpression of Sesn3 augmented the effect of ethanol on phospho-p70 S6 kinase. The levels of hepatic light chain 3, a marker for autophagy, expression were significantly decreased in ethanol-fed mice after Sesn3 gene was knocked down. Our findings suggest that inhibitory effect of ethanol on Sesn3 may play an important role in the development of ethanolinduced fatty liver.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume307
Issue number1
DOIs
StatePublished - Jul 1 2014

Fingerprint

Ethanol
Liver
Wounds and Injuries
Triglycerides
70-kDa Ribosomal Protein S6 Kinases
Lipids
AMP-Activated Protein Kinases
Autophagy
Fatty Liver
Lipid Metabolism
Small Interfering RNA
Genes
Hepatocytes
Down-Regulation
Alcohols
Gene Expression
Light

Keywords

  • Alcohol
  • Sestrin3
  • Steatosis

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

The inhibitory effect of ethanol on Sestrin3 in the pathogenesis of ethanol-induced liver injury. / Kang, Xinqin; Petyaykina, Kateryna; Tao, Rongya; Xiong, Xiwen; Dong, X.; Liangpunsakul, Suthat.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 307, No. 1, 01.07.2014.

Research output: Contribution to journalArticle

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