| First Author | Rahman SM | Year | 2013 |
| Journal | Biochem Biophys Res Commun | Volume | 430 |
| Issue | 1 | Pages | 336-9 |
| PubMed ID | 23159614 | Mgi Jnum | J:193736 |
| Mgi Id | MGI:5469505 | Doi | 10.1016/j.bbrc.2012.11.027 |
| Citation | Rahman SM, et al. (2013) CCAAT/enhancer binding protein beta deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis. Biochem Biophys Res Commun 430(1):336-9 |
| abstractText | 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/EBPbeta) 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/EBPbeta expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBPbeta 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/EBPbeta(-/-) mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBPbeta(-/-) 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/EBPbeta 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/EBPbeta 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. |
