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

Content Provider	Springer Nature : BioMed Central
Author	Tsai, Ching-Chou Chen, Yu-Jen Yu, Hong-Ren Huang, Li-Tung Tain, You-Lin Lin, I-Chun Sheen, Jiunn-Ming Wang, Pei-Wen Tiao, Mao-Meng
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.
Related Links	https://lipidworld.biomedcentral.com/counter/pdf/10.1186/s12944-020-01274-y.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s12944-020-01274-y
Journal	Lipids in Health and Disease
Issue Number	1
Volume Number	19
Language	English
Publisher	BioMed Central
Publisher Date	2020-05-25
Access Restriction	Open
Subject Keyword	Lipidology Medical Biochemistry Clinical Nutrition Acetylcysteine Steatosis Liver ER stress
Content Type	Text
Resource Type	Article
Subject	Endocrinology Clinical Biochemistry Endocrinology, Diabetes and Metabolism Biochemistry (medical)
Journal Impact Factor	3.9/2023
5-Year Journal Impact Factor	4.3/2023

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