Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons.
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.
Beigneux
Anne P
AP
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
Davies
Brandon S J
BS
Gin
Peter
P
Weinstein
Michael M
MM
Farber
Emily
E
Qiao
Xin
X
Peale
Franklin
F
Bunting
Stuart
S
Walzem
Rosemary L
RL
Wong
Jinny S
JS
Blaner
William S
WS
Ding
Zhi-Ming
ZM
Melford
Kristan
K
Wongsiriroj
Nuttaporn
N
Shu
Xiao
X
de Sauvage
Fred
F
Ryan
Robert O
RO
Fong
Loren G
LG
Bensadoun
André
A
Young
Stephen G
SG
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
D002914:Chylomicrons; C472779:GPI-HBP1 protein, mouse; D018110:Receptors, Lipoprotein; D008071:Lipoprotein Lipase