CCAAT/enhancer binding protein β deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis

Shaikh M. Rahman, Mahua Choudhury, Rachel C. Janssen, Karalee C. Baquero, Makoto Miyazaki, Jacob E. Friedman

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) is an important regulator of liver gene expression but little is known about its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBPβ expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBPβ deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBPβ-/- mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBPβ-/- mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBPβ in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBPβ might therefore be an important therapeutic strategy to prevent LXR activation-mediated adverse effects on liver TG metabolism without disrupting its beneficial effects on cholesterol metabolism.

Original languageEnglish
Pages (from-to)336-339
Number of pages4
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - Jan 4 2013


  • Cholesterol efflux
  • LXR agonist
  • Lipogenesis
  • Mitochondrial function
  • Steatosis


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