The expression of GPIHBP1, an endothelial cell binding site for lipoprotein lipase and chylomicrons, is induced by peroxisome proliferator-activated receptor-gamma.
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.
Davies
Brandon S J
BS
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA. bdavies@mednet.ucla.edu
Waki
Hironori
H
Beigneux
Anne P
AP
Farber
Emily
E
Weinstein
Michael M
MM
Wilpitz
Damien C
DC
Tai
Li-Jung
LJ
Evans
Ronald M
RM
Fong
Loren G
LG
Tontonoz
Peter
P
Young
Stephen G
SG
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
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
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