C/EBP beta and C/EBP delta expression is elevated in the early phase of ethanol-induced hepatosteatosis in mice.
OBJECTIVE
Alcohol, which is predominantly metabolized in the liver, is a major hepatic toxicant that readily induces hepatic steatosis. The expression of CCAAT enhancer binding protein (C/EBP), especially the C/EBP delta variety, is increased in the early phase of adipogenesis. However, the role of C/EBP delta in ethanol-induced hepatosteatosis is unclear.


METHODS
Male C57BL/6J mice were randomized to one of four groups: a control group, a group receiving orally administered ethanol (4 g ethanol/kg body weight) (EtOH), a high-fat-diet (HF) group and an EtOH+HF group. Mice were sacrificed after 5 or 10 weeks for various measurements. The in vitro effect of ethanol on the expression of C/EBP alpha, beta and delta was studied in HepG2 cells.


RESULTS
By week 5, ethanol treatment had significantly increased liver C/EBP delta and beta protein expression (by 2.3- and 1.4-fold, respectively), which then returned to the control level by week 10. In contrast, the expression of C/EBP alpha was evident only at week 10. The in vitro study shows that C/EBP delta expression was elevated significantly at 24 h but not at 48 or 72 h. C/EBP beta expression was highest at 48 h, whereas C/EBP alpha expression was highest at 72 h. We also found that a low concentration of ethanol plus oleic acid enhanced C/EBP delta expression in HepG2 cells.


CONCLUSIONS
C/EBP delta expression appears to play an important role in the early phase of ethanol-induced hepatosteatosis in mice and in ethanol-treated HepG2 cells. In addition, EtOH+HF enhances the expression of C/EBP delta in HepG2 cells. Thus, C/EBP delta might be a therapeutic target in alcoholic hepatosteatosis.
Chen
Yu-hsuan
YH
Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taiwan, China.
Yang
Chih-min
CM
Chang
Shih-pei
SP
Hu
Miao-lin
ML
D050156:Adipogenesis; D000818:Animals; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D000431:Ethanol / Q000009:adverse effects*; D005234:Fatty Liver / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019301:Oleic Acid / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D051743:CCAAT-Enhancer-Binding Protein-delta; D019301:Oleic Acid; D000431:Ethanol