SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice

Chih Wei Liu, Chia Chang Huang, Chien Fu Hsu, Tzu Hao Li, Yu Lien Tsai, Ming Wei Lin, Hung Cheng Tsai, Shiang Fen Huang, Ying Ying Yang*, Yun Cheng Hsieh, Tzung Yan Lee, Chang Youh Tsai, Yi Hsiang Huang, Ming Chih Hou, Han Chieh Lin

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

9 Scopus citations

Abstract

Background In non-alcoholic steatohepatitis (NASH), muscle wasting was an aggravating factor for the progression of hepatic steatosis. This study explores the potential benefits of chronic treatment with resveratrol, a strong activator of SIRT1 on the muscle wasting of NASH mice. Methods In vivo and in vitro study, we evaluate the SIRT1-dependent mechanisms and effects of resveratrol administration for 6 weeks with high-fat-methionine and choline deficient diet-induced NASH mice and palmitate-pretreated C2C12 myoblast cells. Results Resveratrol treatment improved grip strength and muscle mass of limbs, increased running distance and time on exercise wheels in NASH mice. There is a negative correlation between muscular SIRT1 activity and 3-nitrotyrosine levels of NASH and NASH-resv mice. The SIRT1-dependent effect of muscle wasting was associated with the suppression of oxidative stress, upregulation of antioxidants, inhibition of protein degradation, activation of autophagy, suppression of apoptotic activity, upregulation of lipolytic genes and the reduction of fatty infiltration in limb muscles of NASH mice. In vitro, resveratrol alleviated palmitate acid-induced oxidative stress, lipid deposition, autophagy dysfunction, apoptotic signals, and subsequently reduced fusion index and myotube formation of C2C12 cells. The beneficial effects of resveratrol were abolished by EX527. Conclusions Our study suggests that chronic resveratrol treatment is a potential strategy for amelioration of hepatic steatosis and muscle wasting in NASH mouse model.

Original languageEnglish
Article numbere000381
JournalBMJ Open Gastroenterology
Volume7
Issue number1
DOIs
StatePublished - 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 BMJ Publishing Group. All rights reserved.

Keywords

  • apoptosis
  • nonalcoholic steatohepatitis
  • oxidative stress
  • signalling

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