CCAAT/enhancer binding protein deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis. Academic Article uri icon


  • 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/EBP) 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/EBP expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBP 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/EBP(-/-) mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBP(-/-) 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/EBP 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/EBP 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.

published proceedings

  • Biochem Biophys Res Commun

author list (cited authors)

  • Rahman, S. M., Choudhury, M., Janssen, R. C., Baquero, K. C., Miyazaki, M., & Friedman, J. E.

citation count

  • 7

complete list of authors

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

publication date

  • January 2013