Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1 Plays a Critical Role in the Lipolytic Processing of Chylomicrons

Anne P Beigneux; Brandon S.J Davies; Peter Gin; Michael M Weinstein; Emily Farber; Xin Qiao; Franklin Peale; Stuart Bunting; Rosemary L Walzem; Jinny S Wong; William S Blaner; Zhi-Ming Ding; Kristan Melford; Nuttaporn Wongsiriroj; Xiao Shu; Fred de Sauvage; Robert O Ryan; Loren G Fong; André Bensadoun; Stephen G Young

doi:10.1016/j.cmet.2007.02.002

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Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1 Plays a Critical Role in the Lipolytic Processing of Chylomicrons

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Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1 Plays a Critical Role in the Lipolytic Processing of Chylomicrons

Anne P Beigneux, Brandon S.J Davies, Peter Gin, Michael M Weinstein, Emily Farber, Xin Qiao, Franklin Peale, Stuart Bunting, Rosemary L Walzem, Jinny S Wong, …

Cell metabolism, Vol.5(4), pp.279-291

2007

DOI: 10.1016/j.cmet.2007.02.002

PMCID: PMC1913910

PMID: 17403372

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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.

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Title: Subtitle: Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1 Plays a Critical Role in the Lipolytic Processing of Chylomicrons
Creators: Anne P Beigneux - Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Brandon S.J Davies - Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Peter Gin - Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Michael M Weinstein - Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Emily Farber - Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Xin Qiao - Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Franklin Peale - Genentech, One DNA Way, South San Francisco, CA 94080, USA
Stuart Bunting - Genentech, One DNA Way, South San Francisco, CA 94080, USA
Rosemary L Walzem - Departments of Poultry Science and Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA
Jinny S Wong - Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA
William S Blaner - Department of Medicine, Columbia University, New York, NY 10032, USA
Zhi-Ming Ding - Lexicon Genetics, 8800 Technology Forest Place, The Woodlands, TX 77381, USA
Kristan Melford - Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA
Nuttaporn Wongsiriroj - Department of Medicine, Columbia University, New York, NY 10032, USA
Xiao Shu - Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA
Fred de Sauvage - Genentech, One DNA Way, South San Francisco, CA 94080, USA
Robert O Ryan - Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA
Loren G Fong - Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
André Bensadoun - Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA
Stephen G Young - Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Resource Type: Journal article
Publication Details: Cell metabolism, Vol.5(4), pp.279-291
Publisher: Elsevier Inc
DOI: 10.1016/j.cmet.2007.02.002
PMID: 17403372
PMCID: PMC1913910
ISSN: 1550-4131
eISSN: 1932-7420
Language: English
Date published: 2007
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984024555502771

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