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Journal of Lipid Research, Vol. 50, S57-S62, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Enzymology

GPIHBP1, a GPI-anchored protein required for the lipolytic processing of triglyceride-rich lipoproteins

Anne P. Beigneux^1,*, Brandon S. J. Davies^*, André Bensadoun, Loren G. Fong^1, and Stephen G. Young^1,*,

^* Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
Division of Nutritional Science, Cornell University, Ithaca, NY 14853

This study was supported by National Institutes of Health (NIH) Grants 5P01HL090553-02 and 5R01HL087228-02 (to S.G.Y), an American Heart Association Scientist Development Award (to A.P.B.).

Conflict of interest: The authors have declared that no conflict of interest exists.

Published, JLR Papers in Press, October 14, 2008.

¹ To whom correspondence should be addressed. e-mail: abeigneux{at}mednet.ucla.edu (A.P.B.); lfong{at}mednet.ucla.edu (L.G.F.); sgyoung{at}mednet.ucla.edu (S.G.Y.)

ABSTRACT

GPIHBP1, a small glycosylphosphatidylinositol-anchored glycoprotein, is required for the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1 knockout mice exhibit chylomicronemia, even on a low-fat diet, with plasma triglyceride levels of 3,500–5,000 mg/dl. GPIHBP1 is expressed highly in heart, adipose tissue, and skeletal muscle, the same tissues that express high levels of lipoprotein lipase (LPL). In each of these tissues, GPIHBP1 is located in capillary endothelial cells. Chinese hamster ovary (CHO) cells transfected with a GPIHBP1 expression vector bind LPL and chylomicrons avidly. The expression of GPIHBP1 in mice is modulated by fasting and refeeding and is also regulated by peroxisome proliferator-activated receptor (PPAR) agonists. Here, we review recent progress in understanding GPIHBP1 and discuss its role in lipolysis.

Supplementary key words chylomicrons • lipoprotein lipase • endothelial • PPAR • glycosylphosphatidylinositol

Abbreviations: CHO, Chinese hamster ovary; GPI, glycosylphosphatidylinositol; LPL, lipoprotein lipase; Ly6, lymphocyte antigen 6; PPAR, peroxisome proliferator-activated receptor; UPAR, urokinase-type plasminogen activator receptor

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