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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 586 - 594 (9page)
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Obesity and binge drinking often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. In this mini-review, we briefly summarize clinical evidence of the synergistical effect of obesity and heavy drinking on steatohepatitis and discuss the underlying mechanisms obtained from the study of several mouse models. High-fat diet (HFD) feeding and binge ethanol synergistically induced steatohepatitis and fibrosis in mice with significant intrahepatic neutrophil infiltration; such HFD-plus-ethanol treatment markedly up-regulated the hepatic expression of many chemokines with the highest fold (approximately 30-fold) induction of chemokine (C-X-C motif) ligand 1 (Cxcl1), which contributes to hepatic neutrophil infiltration and liver injury. Furthermore, HFD feeding activated peroxisome proliferator-activated receptor gamma that subsequently inhibited CXCL1 upregulation in hepatocytes, thereby forming a negative feedback loop to prevent neutrophil overaction; whereas binge ethanol blocked this loop and then exacerbated CXCL1 elevation, neutrophil infiltration, and liver injury. Interestingly, inflamed mouse hepatocytes attracted neutrophils less effectively than inflamed human hepatocytes due to the lower induction of CXCL1 and the lack of the interleukin (IL)-8 gene in the mouse genome, which may be one of the reasons for difficulty in development of mouse models of alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH). Hepatic overexpression of Cxcl1 and/or IL-8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing neutrophil infiltration, oxidative stress, hepatocyte death, fibrosis, and p38 mitogen-activated protein kinase activation. Collectively, obesity and binge drinking synergistically promote steatohepatitis via the induction of CXCL1 and subsequent hepatic neutrophil infiltration.
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참고문헌 (64)
참고문헌 신청
Parker R / 2018 / Alcohol, adipose tissue and liver disease : mechanistic links and clinical considerations / Nat Rev Gastroenterol Hepatol 15:50~59
Parker R / 2019 / Obesity in acute alcoholic hepatitis increases morbidity and mortality / EBioMedicine 45:511~518
Inbeom Kwon / 2019 / Effects of Moderate Alcohol Drinking in Patients with Nonalcoholic Fatty Liver Disease / Gut and Liver 13(3):308~314
Ajmera VH / 2017 / Is moderate alcohol use in nonalcoholic fatty liver disease good or bad? A critical review / Hepatology 65:2090~2099
Xu J / 2011 / Synergistic steatohepatitis by moderate obesity and alcohol in mice despite increased adiponectin and p-AMPK / J Hepatol 55:673~682
Parker R / 2019 / Obesity in acute alcoholic hepatitis increases morbidity and mortality / EBioMedicine 45:511~518
Inbeom Kwon / 2019 / Effects of Moderate Alcohol Drinking in Patients with Nonalcoholic Fatty Liver Disease / Gut and Liver 13(3):308~314
Ajmera VH / 2017 / Is moderate alcohol use in nonalcoholic fatty liver disease good or bad? A critical review / Hepatology 65:2090~2099
Xu J / 2011 / Synergistic steatohepatitis by moderate obesity and alcohol in mice despite increased adiponectin and p-AMPK / J Hepatol 55:673~682
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