title: The expression of GPIHBP1, an endothelial cell binding site for lipoprotein lipase and chylomicrons, is induced by peroxisome proliferator-activated receptor-gamma.
abstract: Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a protein in the lymphocyte antigen 6 (Ly-6) family, plays a key role in the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1 binds lipoprotein lipase and chylomicrons and is expressed along the luminal surface of microvascular endothelial cells. Lipolysis is known to be regulated by metabolic factors and is controlled at multiple levels, including the number of LPL binding sites on capillaries. Here, we tested the possibility that GPIHBP1 expression could be regulated by dietary perturbations and by peroxisome proliferator-activated receptors (PPARs). Gpihbp1 transcript levels in the heart and in brown and white adipose tissue increased with fasting and returned toward baseline after refeeding. A PPARgamma agonist increased Gpihbp1 expression in adipose tissue, heart, and skeletal muscle, whereas PPARalpha and PPARdelta agonists had no effect. Gpihbp1 was expressed in endothelial cells of embryoid bodies generated from mouse embryonic stem cells, and Gpihbp1 expression in embryoid bodies was up-regulated by a PPARgamma agonist. Sequences upstream from exon 1 of Gpihbp1 contain a strong PPAR binding site, and that site exhibited activity in a luciferase reporter assay. Gpihbp1 transcript levels in brown and white adipose tissue were lower in endothelial cell PPARgamma knockout mice than in littermate control mice, suggesting that PPARgamma regulates Gpihbp1 expression in vivo. We conclude that GPIHBP1 is regulated by dietary factors and by PPARgamma.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA. bdavies@mednet.ucla.edu
authors.forename: Brandon S J
authors.initials: BS
authors.lastname: Davies
authors.forename: Hironori
authors.initials: H
authors.lastname: Waki
authors.forename: Anne P
authors.initials: AP
authors.lastname: Beigneux
authors.forename: Emily
authors.initials: E
authors.lastname: Farber
authors.forename: Michael M
authors.initials: MM
authors.lastname: Weinstein
authors.forename: Damien C
authors.initials: DC
authors.lastname: Wilpitz
authors.forename: Li-Jung
authors.initials: LJ
authors.lastname: Tai
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002914:Chylomicrons / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D053595:Embryonic Stem Cells / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005215:Fasting / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D011401:Promoter Regions, Genetic; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D018110:Receptors, Lipoprotein / Q000235:genetics* / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D002914:Chylomicrons; D017931:DNA Primers; D004041:Dietary Fats; C472779:GPI-HBP1 protein, mouse; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008071:Lipoprotein Lipase
references.citation: J Lipid Res. 1996 Apr;37(4):693-707
references.pmid: 8732771
references.citation: Biochem J. 2001 Apr 1;355(Pt 1):105-11
references.pmid: 11256954
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15712-7
references.pmid: 14660788
references.citation: Prog Lipid Res. 2006 Mar;45(2):120-59
references.pmid: 16476485
references.citation: Cell. 1998 Apr 17;93(2):241-52
references.pmid: 9568716
references.citation: Cell Metab. 2007 Apr;5(4):279-91
references.pmid: 17403372
references.citation: Genes Dev. 2007 Aug 1;21(15):1895-908
references.pmid: 17652179
references.citation: J Mol Med (Berl). 2002 Dec;80(12):753-69
references.pmid: 12483461
references.citation: Methods Enzymol. 2003;365:228-41
references.pmid: 14696349
references.citation: Curr Opin Lipidol. 2007 Aug;18(4):389-96
references.pmid: 17620854
references.citation: J Clin Invest. 1999 Jun;103(11):1489-98
references.pmid: 10359558
references.citation: Annu Rev Med. 2002;53:409-35
references.pmid: 11818483
references.citation: Genes Dev. 1994 May 15;8(10):1224-34
references.pmid: 7926726
references.citation: Cell. 1995 Dec 1;83(5):803-12
references.pmid: 8521497
references.citation: EMBO J. 1996 Oct 1;15(19):5336-48
references.pmid: 8895578
references.citation: Am J Physiol Endocrinol Metab. 2000 Feb;278(2):E211-8
references.pmid: 10662704
references.citation: Nat Med. 2007 Dec;13(12):1496-503
references.pmid: 18059282
references.citation: Nucleic Acids Res. 2003 Jul 15;31(14):e73
references.pmid: 12853650
references.citation: J Biol Chem. 1998 Jul 3;273(27):16710-4
references.pmid: 9642225