title: Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons.
abstract: The triglycerides in chylomicrons are hydrolyzed by lipoprotein lipase (LpL) along the luminal surface of the capillaries. However, the endothelial cell molecule that facilitates chylomicron processing by LpL has not yet been defined. Here, we show that glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a critical role in the lipolytic processing of chylomicrons. Gpihbp1-deficient mice exhibit a striking accumulation of chylomicrons in the plasma, even on a low-fat diet, resulting in milky plasma and plasma triglyceride levels as high as 5000 mg/dl. Normally, Gpihbp1 is expressed highly in heart and adipose tissue, the same tissues that express high levels of LpL. In these tissues, GPIHBP1 is located on the luminal face of the capillary endothelium. Expression of GPIHBP1 in cultured cells confers the ability to bind both LpL and chylomicrons. These studies strongly suggest that GPIHBP1 is an important platform for the LpL-mediated processing of chylomicrons in capillaries.
authors.affiliation: Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, and Children's Hospital Oakland Research Institute 94609, USA. abeigneux@mednet.ucla.edu
authors.forename: Anne P
authors.initials: AP
authors.lastname: Beigneux
authors.forename: Brandon S J
authors.initials: BS
authors.lastname: Davies
authors.forename: Peter
authors.initials: P
authors.lastname: Gin
authors.forename: Michael M
authors.initials: MM
authors.lastname: Weinstein
authors.forename: Emily
authors.initials: E
authors.lastname: Farber
authors.forename: Xin
authors.initials: X
authors.lastname: Qiao
authors.forename: Franklin
authors.initials: F
authors.lastname: Peale
authors.forename: Stuart
authors.initials: S
authors.lastname: Bunting
authors.forename: Rosemary L
authors.initials: RL
authors.lastname: Walzem
authors.forename: Jinny S
authors.initials: JS
authors.lastname: Wong
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Ding
authors.forename: Kristan
authors.initials: K
authors.lastname: Melford
authors.forename: Nuttaporn
authors.initials: N
authors.lastname: Wongsiriroj
authors.forename: Xiao
authors.initials: X
authors.lastname: Shu
authors.forename: Fred
authors.initials: F
authors.lastname: de Sauvage
authors.forename: Robert O
authors.initials: RO
authors.lastname: Ryan
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
authors.forename: André
authors.initials: A
authors.lastname: Bensadoun
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
mesh_terms: D000818:Animals; D016466:CHO Cells; D002914:Chylomicrons / Q000097:blood / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004435:Eating / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D008066:Lipolysis / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D011817:Rabbits; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
chemical_list: D002914:Chylomicrons; C472779:GPI-HBP1 protein, mouse; D018110:Receptors, Lipoprotein; D008071:Lipoprotein Lipase