Acta Pharmacologica Sinica (2009) 30: 1138-1143; doi: 10.1038/aps.2009.109

Acta Pharmacologica Sinica (2009) 30: 1138-1143; doi: 10.1038/aps.2009.109; published online 20 July 2009

Original Article

C/EBP beta and C/EBP delta expression is elevated in the early phase of ethanol-induced hepatosteatosis in mice

Yu-hsuan CHEN^{1, 3}, Chih-min YANG³, Shih-pei CHANG²,Miao-lin HU^3,*

¹Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taiwan, China; ²Department of Physical Education, Central Taiwan University of Science and Technology, Taiwan, China; ³Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, China

Aim: 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.

Conclusion: 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.

Keywords: C/EBP delta; ethanol; hepatosteatosis; adipogenesis

This work was supported by grants from the Central Taiwan University of Science and Technology (CTU-96-23 to Yu-hsuan CHEN and Shih-pei CHANG).

* To whom correspondence should be addressed.
Email mlhuhu@nchu.edu.tw
Received 2009-03-23 Accepted 2009-06-12

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