Long term N-acetylcysteine administration rescues liver steatosis via endoplasmic reticulum stress with unfolded protein response in mice

Ching Chou Tsai, Yu Jen Chen, Hong Ren Yu, Li Tung Huang, You Lin Tain, I. Chun Lin, Jiunn Ming Sheen, Pei Wen Wang, Mao Meng Tiao*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

20 Scopus citations

Abstract

Background: Fat accumulation in the liver contributes to the development of non-alcoholic fatty liver disease (NAFLD). N-acetylcysteine (NAC) is an antioxidant, acting both directly and indirectly via upregulation of cellular antioxidants. We examined the mechanisms of liver steatosis after 12 months high fat (HF) diet and tested the ability of NAC to rescue liver steatosis. Methods: Seven-week-old C57BL/6 (B6) male mice were administered HF diet for 12 months (HF group). Two other groups received HF diet for 12 months accompanied by NAC for 12 months (HFD + NAC(1-12)) or 6 months (HFD + NAC(1-6)). The control group was fed regular diet for 12 months (CD group). Results: Liver steatosis was more pronounced in the HF group than in the CD group after 12 month feeding. NAC intake for 6 or 12 months decreased liver steatosis in comparison with HF diet (p < 0.05). Furthermore, NAC treatment also reduced cellular apoptosis and caspase-3 expression. In the unfolded protein response (UPR) pathway, the expression of ECHS1, HSP60, and HSP70 was decreased in the HFD group (p < 0.05) and rescued by NAC therapy. With regards to the endoplasmic reticulum (ER) stress, Phospho-PERK (p-PERK) and ATF4 expression was decreased in the HF group, and only the HFD + NAC(1-12), but not HFD + NAC(1-6) group, showed significant improvement. Conclusion: HF diet for 12 months induces significant liver steatosis via altered ER stress and UPR pathway activity, as well as liver apoptosis. NAC treatment rescues the liver steatosis and apoptosis induced by HF diet.

Original languageEnglish
Article number105
JournalLipids in Health and Disease
Volume19
Issue number1
DOIs
StatePublished - 25 05 2020

Bibliographical note

Publisher Copyright:
© 2020 The Author(s).

Keywords

  • Acetylcysteine
  • ER stress
  • Liver
  • Steatosis

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