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

Tae Hyung Kim, Dahee Choi, Joo Young Kim, Jeong Hyeon Lee, Seung-Hoi Koo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Acetaminophen (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. Methods: Two groups of mice, normal chow (NC) diet-fed and fast food (FF) diet-fed mice for 14weeks, 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. Results: Alanine aminotransferase (ALT) level (199.0±39.0 vs. 63.8±7.4IU/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±185.1IU/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. Conclusions: Our 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.

Original languageEnglish
Article number124
JournalBMC Gastroenterology
Volume17
Issue number1
DOIs
Publication statusPublished - 2017 Nov 28

Fingerprint

Fast Foods
Acetaminophen
Diet
Liver
Wounds and Injuries
Peroxisome Proliferator-Activated Receptors
Alanine Transaminase
Anti-Inflammatory Agents
Cytochrome P-450 CYP2E1
Fatty Liver
Non-alcoholic Fatty Liver Disease
Causality
Liver Diseases
Chronic Disease
Necrosis
Western Blotting
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Acetaminophen
  • Drug-induced liver injury
  • Non-alcoholic fatty liver disease
  • Peroxisome proliferator-activated receptor gamma

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Fast food diet-induced non-alcoholic fatty liver disease exerts early protective effect against acetaminophen intoxication in mice. / Kim, Tae Hyung; Choi, Dahee; Kim, Joo Young; Lee, Jeong Hyeon; Koo, Seung-Hoi.

In: BMC Gastroenterology, Vol. 17, No. 1, 124, 28.11.2017.

Research output: Contribution to journalArticle

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abstract = "Background: Acetaminophen (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. Methods: Two groups of mice, normal chow (NC) diet-fed and fast food (FF) diet-fed mice for 14weeks, 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. Results: Alanine aminotransferase (ALT) level (199.0±39.0 vs. 63.8±7.4IU/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±185.1IU/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. Conclusions: Our 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.",
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AU - Lee, Jeong Hyeon

AU - Koo, Seung-Hoi

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