| First Author | Guan M | Year | 2011 |
| Journal | Hepatology | Volume | 53 |
| Issue | 2 | Pages | 458-66 |
| PubMed ID | 21274867 | Mgi Jnum | J:308390 |
| Mgi Id | MGI:6714328 | Doi | 10.1002/hep.24066 |
| Citation | Guan M, et al. (2011) Hepatocyte nuclear factor-4 alpha regulates liver triglyceride metabolism in part through secreted phospholipase A(2) GXIIB. Hepatology 53(2):458-66 |
| abstractText | UNLABELLED: Hepatocyte nuclear factor-4 alpha (HNF-4alpha) is an important transcription factor governing the expression of genes involved in multiple metabolic pathways. Secreted phospholipase A(2) GXIIB (PLA(2) GXIIB) is an atypical member of a class of secreted phospholipases A(2) . We establish in this study that PLA(2) GXIIB is an HNF-4alpha target gene. We demonstrate that HNF-4alpha binds to a response element on the PLA(2) GXIIB promoter. Moreover, HNF-4alpha agonists induce PLA(2) GXIIB expression in human hepatocarcinoma cells. Importantly, PLA(2) GXIIB-null mice accumulate triglyceride, cholesterol, and fatty acids in the liver and develop severe hepatosteatosis resembling some of the phenotypes of liver-specific HNF-4alpha-null mice. These defects are in part due to compromised hepatic very low-density lipoprotein secretion. Finally, adenovirus-mediated overexpression of HNF-4alpha elevates serum triglyceride level in wild-type but not PLA(2) GXIIB-null mice. CONCLUSION: Collectively, these evidences suggest that HNF-4alpha is a key physiological PLA(2) GXIIB transcriptional regulator and that PLA(2) GXIIB is a novel mediator of triglyceride metabolism in the liver. |
