Hepatic expression of CCAAT/enhancer binding protein alpha: hormonal and metabolic regulation in rats

Diabetologia. 1997 Oct;40(10):1117-24. doi: 10.1007/s001250050796.


There is a significant body of evidence which suggests that the alpha-isoform of the CCAAT/enhancer binding protein (C/EBP alpha) plays a central regulatory role in energy metabolism in the liver. However, there is little information available regarding regulation of its expression in this tissue. In this study, we examined the effect of hormones and diabetes on its expression in rat H4IIE hepatoma cells and in rat liver. Treatment of H4IIE cells with dexamethasone led to a threefold increase in C/EBP alpha mRNA within 4 h. Insulin treatment produced a bi-phasic response, initially reducing mRNA levels up to the 4 h time point, but after 8 h a twofold increase in C/EBP alpha mRNA was observed. Treatment with 8-chlorophenylthio-cAMP produced a twofold induction of C/EBP alpha mRNA after 8 h. Western analysis indicated that the changes in mRNA in response to hormonal treatment generally resulted in corresponding alterations in C/EBP alpha protein levels. Finally, we observed an inhibition of C/EBP alpha gene expression in streptozotocin-diabetic rat liver, reflected by a decrease in both mRNA and protein levels that were partially reversed by insulin treatment. These results indicate that the expression of C/EBP alpha in liver is under complex control by both hormonal and metabolic signals, which is consistent with its role as a trans -regulator of genes which play a role in energy metabolism.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CCAAT-Enhancer-Binding Proteins
  • Cyclic AMP / administration & dosage
  • Cyclic AMP / analogs & derivatives*
  • Cyclic AMP / pharmacology
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / genetics
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / pathology
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / genetics*
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Liver / chemistry*
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Nuclear Proteins / analysis*
  • Nuclear Proteins / drug effects
  • Nuclear Proteins / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Thionucleotides / administration & dosage
  • Thionucleotides / pharmacology*
  • Time Factors
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • Tumor Cells, Cultured


  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Nuclear Proteins
  • RNA, Messenger
  • Thionucleotides
  • Transcription Factors
  • 8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
  • Cyclic AMP