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

Abstract

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 sacrifi ced 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 signifi cantly 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 signifi cantly 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.

Moderate Alcohol Induces Stress Proteins HSF1 and hsp70 and Inhibits Proinflammatory Cytokines Resulting in Endotoxin Tolerance

“…Interestingly, our results show induction of HSF1 mRNA expression by alcohol exposure even in cells subsequently stimulated by LPS indicating alcohol-mediated regulation of HSF1 at the transcriptional level. Transcription factor C/EBPβ has been implicated in induction of HSF1 expression in colonic epithelial cells (45) and upregulation of C/EBPβ protein in response to chronic alcohol exposure has been demonstrated in mouse liver and hepatic nuclear extracts (46, 47). Therefore it is plausible that HSF1 mRNA induction by alcohol may be regulated by C/EBPβ in monocytes/macrophages.…”

Coordinated Dynamic Gene Expression Changes in the Central Nucleus of the Amygdala During Alcohol Withdrawal

“…CeA‐specific promoter sequence analysis identified binding sites for TFs that potentially contribute to the observed expression patterns. Of note, Cebp (Cluster 1) (Chen et al., ), Usf‐1 (Cluster 1) (Potter et al., ), and Smad3 (Cluster 3) (Karaa et al., ) have been implicated in mediating alcoholic liver disease. Additionally, Usf‐1 and Ap‐2 (Clusters 2 and 4, respectively) are known to regulate the expression of monoaminergic neurotransmitter‐associated genes including tyrosine hydroxylase and dopamine beta hydroxylase (Hong et al., ; Kim et al., ,b; Schmidt et al., ).…”

The Visualization of the Space Probability Distribution for a Moving Particle: In a Single Ring-Shaped Coulomb Potential

“…Since the ring-shaped non-central potentials have potential applications in quantum chemistry and nuclear physics, e.g., they might describe the molecular structure of Benzene and interaction between the deformed nucleuses, it is not surprising that the relevant investigations for them have attracted many attentions [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Based on previous study, we have known that this type of ring-shaped non-central potentials can be solved in spherical coordinates and also the system Hamiltonian with the hidden symmetry makes the bound state energy levels possess an "accidental" degeneracy, which arises from the SU(2) invariance of the Schrödinger Hamiltonian [1].…”