title: Oxysterol binding protein induces upregulation of SREBP-1c and enhances hepatic lipogenesis.
abstract: BACKGROUND
  Oxysterol binding protein (OSBP) has previously been implicated as a sterol sensor that regulates sphingomyelin synthesis and the activity of extracellular signal-regulated kinases (ERK).
  
  
  RESULTS
  We determined the effects of adenovirus-mediated hepatic overexpression of OSBP and its homologues ORP1L and ORP3 on mouse serum lipids. Whereas ORP1L and ORP3 had no effect on serum lipids, OSBP induced a marked increase of VLDL triglycerides (TG). Also, the liver tissue TG were elevated in the AdOSBP-injected mice, and their TG secretion rate was increased by 70%. The messenger RNAs for enzymes of fatty acid synthesis and their transcriptional regulator, SREBP-1c, as well as the Insig-1 mRNA, were upregulated two-fold in the OSBP-expressing livers. No change occurred in the messages of liver X receptor target genes ABCA1, ABCG5, and CYP7A1, and the Insig-2a mRNA was reduced. The phosphorylation of ERK was decreased in AdOSBP-infected liver and cultured hepatocytes. Importantly, silencing of OSBP in hepatocytes suppressed the induction of SREBP1-c by insulin and resulted in a reduction of TG synthesis.
  
  
  CONCLUSIONS
  Our results demonstrate that OSBP regulates hepatic TG metabolism and suggest the involvement of OSBP in the insulin signaling pathways that control hepatic lipogenesis.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute, Biomedicum, P.O.Box 104, FI-00251 Helsinki, Finland.
authors.forename: Daoguang
authors.initials: D
authors.lastname: Yan
authors.forename: Markku
authors.initials: M
authors.lastname: Lehto
authors.forename: Laura
authors.initials: L
authors.lastname: Rasilainen
authors.forename: Jari
authors.initials: J
authors.lastname: Metso
authors.forename: Christian
authors.initials: C
authors.lastname: Ehnholm
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Vesa M
authors.initials: VM
authors.lastname: Olkkonen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D015243:Cholesterol, VLDL / Q000097:blood; D050556:Fatty Acid-Binding Proteins; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050155:Lipogenesis / Q000502:physiology*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics*; D011817:Rabbits; D011987:Receptors, Steroid / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000096:biosynthesis; D015854:Up-Regulation; D000098825:Oxysterol Binding Proteins
chemical_list: D002352:Carrier Proteins; D015243:Cholesterol, VLDL; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; C471934:OSBPL3 protein, human; D012333:RNA, Messenger; D011987:Receptors, Steroid; D014280:Triglycerides; D000098825:Oxysterol Binding Proteins