Abnormal Patterns of Lipoprotein Lipase Release into the Plasma in GPIHBP1-deficient Mice

Michael M Weinstein; Liya Yin; Anne P Beigneux; Brandon S. J Davies; Peter Gin; Kristine Estrada; Kristan Melford; Joseph R Bishop; Jeffrey D Esko; Geesje M Dallinga-Thie; Loren G Fong; André Bensadoun; Stephen G Young

doi:10.1074/jbc.M806067200

Back

Abnormal Patterns of Lipoprotein Lipase Release into the Plasma in GPIHBP1-deficient Mice

Journal article

Open access

Peer reviewed

Abnormal Patterns of Lipoprotein Lipase Release into the Plasma in GPIHBP1-deficient Mice

Michael M Weinstein, Liya Yin, Anne P Beigneux, Brandon S. J Davies, Peter Gin, Kristine Estrada, Kristan Melford, Joseph R Bishop, Jeffrey D Esko, Geesje M Dallinga-Thie, …

The Journal of biological chemistry, Vol.283(50), pp.34511-34518

12/12/2008

DOI: 10.1074/jbc.M806067200

PMCID: PMC2596386

PMID: 18845532

Files and links (1)

url

https://doi.org/10.1074/jbc.M806067200View

Published (Version of record) Open Access

Abstract

GPIHBP1-deficient mice ( Gpihbp1 –/– ) exhibit severe chylomicronemia. GPIHBP1 is located within capillaries of muscle and adipose tissue, and expression of GPIHBP1 in Chinese hamster ovary cells confers upon those cells the ability to bind lipoprotein lipase (LPL). However, there has been absolutely no evidence that GPIHBP1 actually interacts with LPL in vivo . Heparin is known to release LPL from its in vivo binding sites, allowing it to enter the plasma. After an injection of heparin, we reasoned that LPL bound to GPIHBP1 in capillaries would be released very quickly, and we hypothesized that the kinetics of LPL entry into the plasma would differ in Gpihbp1 –/– and control mice. Indeed, plasma LPL levels peaked very rapidly (within 1 min) after heparin in control mice. In contrast, plasma LPL levels in Gpihbp1 –/– mice were much lower 1 min after heparin and increased slowly over 15 min. In keeping with that result, plasma triglycerides fell sharply within 10 min after heparin in wild-type mice, but were negligibly altered in the first 15 min after heparin in Gpihbp1 –/– mice. Also, an injection of Intralipid released LPL into the plasma of wild-type mice but was ineffective in releasing LPL in Gpihbp1 –/– mice. The observed differences in LPL release cannot be ascribed to different tissue stores of LPL, as LPL mass levels in tissues were similar in Gpihbp1 –/– and control mice. The differences in LPL release after intravenous heparin and Intralipid strongly suggest that GPIHBP1 represents an important binding site for LPL in vivo .

Lipids and Lipoproteins

Metabolism, Regulation, and Signaling

Details

Title: Subtitle: Abnormal Patterns of Lipoprotein Lipase Release into the Plasma in GPIHBP1-deficient Mice
Creators: Michael M Weinstein - Departments of
Liya Yin - University of California, Los Angeles
Anne P Beigneux - Departments of
Brandon S. J Davies - Departments of
Peter Gin - Departments of
Kristine Estrada - Departments of
Kristan Melford - Departments of
Joseph R Bishop - Departments of
Jeffrey D Esko - Departments of
Geesje M Dallinga-Thie - Departments of
Loren G Fong - Departments of
André Bensadoun - Departments of
Stephen G Young - Departments of
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.283(50), pp.34511-34518
DOI: 10.1074/jbc.M806067200
PMID: 18845532
PMCID: PMC2596386
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology
Language: English
Date published: 12/12/2008
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984025266902771

Metrics

25 Record Views

67 Times Cited - Web of Science