期刊
JOURNAL OF HEPATOLOGY
卷 50, 期 1, 页码 140-149出版社
ELSEVIER
DOI: 10.1016/j.jhep.2008.08.023
关键词
Steatosis; Free fatty acids; CD95/Fas; Apoptosis; Adiponectin; AdipoR1; AdipoR2; M30; HepG2 cells; HCV
资金
- Deutsche Forschungsgemeinschaft (DFG) [267/4-1]
- Wilhelm Laupitz Foundation
- Federal Ministry of Education and Research (BMBF) [16,4, 01KI0405]
- Marga and Walter Boll Foundation
Background/Aims: Steatosis may trigger hepatocytes to up-regulate CD95/Fas thereby increasing susceptibility to apoptosis, inflammation and fibrosis. We investigated this concept and potential roles of adiponectin and its receptors (AdipoR1; AdipoR2) in chronically HCV-infected patients. Methods: In 98 HCV+ patients and 20 controls, sera were tested for HCV genotypes, FFAs, adiponectin and the M30 apoptosis indicator, and biopsies were evaluated for steatosis/inflammation/fibrosis, CD95/Fas (mRNA/protein), adiponectin (mRNA/protein), AdipoR1/-R2 (mRNA) and M30 (protein). We also questioned whether adiponectin protects HepG2 hepatoblastoma cells from FFA-triggered CD95/Fas up-regulation and apoptosis. Results: Patients [HCV clades 1 (78%), 2 (3%) and 3 (19%)] revealed increased FFA and adiponectin serum levels (p = .005). Hepatocyte CD95/Fas up-regulation correlated with steatosis, inflammation and fibrosis (p = .004). Advanced fibrosis correlated significantly (p = .05) with serum M30. Liver adiponectin correlated with steatosis (p = .016), CD95/Fas (p < .001) and inflammation/fibrosis. Hepatocyte AdipoR2 mRNA specifically correlated with serum adiponectin and steatosis (p = .003), while hepatocyte AdipoR1 mRNA dropped in pronounced fibrosis (p = .060). Finally, adiponectin protected HepG2 cells from FFA-triggered CD95/Fas expression and induction of apoptosis (p = .0396). Conclusions: In chronic HCV infection, steatosis up-regulates hepatocyte CD95/Fas and thus increases apoptosis, which facilitates inflammation and fibrosis. The physiologic countermeasure of adiponectin up-regulation may offer clues for future therapeutic intervention. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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