title: Hepatocyte nuclear factor-4 alpha regulates liver triglyceride metabolism in part through secreted phospholipase A₂ GXIIB.
abstract: Hepatocyte nuclear factor-4 alpha (HNF-4α) 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-4α target gene. We demonstrate that HNF-4α binds to a response element on the PLA(2) GXIIB promoter. Moreover, HNF-4α 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-4α-null mice. These defects are in part due to compromised hepatic very low-density lipoprotein secretion. Finally, adenovirus-mediated overexpression of HNF-4α elevates serum triglyceride level in wild-type but not PLA(2) GXIIB-null mice.
  
  
  CONCLUSIONS
  Collectively, these evidences suggest that HNF-4α is a key physiological PLA(2) GXIIB transcriptional regulator and that PLA(2) GXIIB is a novel mediator of triglyceride metabolism in the liver.
authors.affiliation: Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Science City, China.
authors.forename: Min
authors.initials: M
authors.lastname: Guan
authors.forename: Linbing
authors.initials: L
authors.lastname: Qu
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Tan
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Wong
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054497:Phospholipases A2, Secretory / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D051557:Hepatocyte Nuclear Factor 4; D014280:Triglycerides; D002784:Cholesterol; D054497:Phospholipases A2, Secretory