Fast food diet-induced non-alcoholic fatty liver disease exerts early protective effect against acetaminophen intoxication in mice

BMC Gastroenterology

Research Article

Tae Hyung Kim¹  Joo Young Kim²  Jeong Hyeon Lee²  Dahee Choi³  Seung-Hoi Koo³ 

[1] Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea;Department of Pathology, Korea University College of Medicine, Seoul, South Korea;Division of Life Sciences, Korea University College of Life Sciences & Biotechnology, 145 Anam-Ro Seongbuk-Gu, 02841, Seoul, South Korea;

关键词: Acetaminophen;    Non-alcoholic fatty liver disease;    Drug-induced liver injury;    Peroxisome proliferator-activated receptor gamma;   

DOI  :  10.1186/s12876-017-0680-z

 received in 2017-07-16, accepted in 2017-11-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAcetaminophen (APAP) is a readily available and safe painkiller. However, its overdose is the most common cause of acute liver injury (ALI). Many predisposing factors contribute to susceptibility to APAP-induced ALI. Non-alcoholic fatty liver disease (NAFLD), the major cause of chronic liver disease, is considered an important predictor of APAP-induced ALI, although the exact mechanism controversial. In this study, we aimed to elucidate the effects of NAFLD on APAP-induced ALI.MethodsTwo groups of mice, normal chow (NC) diet-fed and fast food (FF) diet-fed mice for 14 weeks, were further divided into two subgroups: intraperitoneally injected with either saline (NC-S and FF-S groups) or APAP (NC-A and FF-A groups). Biochemical tests, histological analysis, quantitative PCR, and western blotting were conducted.ResultsAlanine aminotransferase (ALT) level (199.0 ± 39.0 vs. 63.8 ± 7.4 IU/L, p < 0.05) and NAFLD activity score (0 vs. 4.5 ± 0.22) were significantly higher in mice in FF-S group than those in NC-S group. ALI features such as ALT level (8447.8 ± 1185.3 vs. 836.6 ± 185.1 IU/L, p < 0.001) and centrizonal necrosis were prominent and mRNA levels of Trib3 (RR, 1.81) was high in mice in the NC-A group. Levels of CYP2E1 and anti-inflammatory molecules such as PPAR-γ, p62, and NRF2 were high in mice in the FF-A group.ConclusionsOur results showed that while the FF diet clearly induced non-alcoholic steatohepatitis and metabolic syndrome, NAFLD also attenuates APAP-induced ALI by inducing anti-inflammatory molecules such as PPAR-γ.

【 授权许可】

CC BY   
© The Author(s). 2017