Apolipoprotein C-III inhibits triglyceride hydrolysis by GPIHBP1-bound LPL[S]

Mikael Larsson; Christopher M. Allan; Rachel S. Jung; Patrick J. Heizer; Anne P. Beigneux; Stephen G. Young; Loren G. Fong

Journal of Lipid Research (Sep 2017)

Apolipoprotein C-III inhibits triglyceride hydrolysis by GPIHBP1-bound LPL[S]

Mikael Larsson,
Christopher M. Allan,
Rachel S. Jung,
Patrick J. Heizer,
Anne P. Beigneux,
Stephen G. Young,
Loren G. Fong

Affiliations

Mikael Larsson: To whom correspondence should be addressed.; Departments of Medicine and Human Genetics, University of California Los Angeles, Los Angeles, CA 90095; To whom correspondence should be addressed.
Christopher M. Allan: Departments of Medicine and Human Genetics, University of California Los Angeles, Los Angeles, CA 90095
Rachel S. Jung: Departments of Medicine and Human Genetics, University of California Los Angeles, Los Angeles, CA 90095
Patrick J. Heizer: Departments of Medicine and Human Genetics, University of California Los Angeles, Los Angeles, CA 90095
Anne P. Beigneux: Departments of Medicine and Human Genetics, University of California Los Angeles, Los Angeles, CA 90095
Stephen G. Young: To whom correspondence should be addressed.; Departments of Medicine and Human Genetics, University of California Los Angeles, Los Angeles, CA 90095; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095; To whom correspondence should be addressed.
Loren G. Fong: To whom correspondence should be addressed.; Departments of Medicine and Human Genetics, University of California Los Angeles, Los Angeles, CA 90095; To whom correspondence should be addressed.

Journal volume & issue: Vol. 58, no. 9
pp. 1893 – 1902

Abstract

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ApoC-III is often assumed to retard the intravascular processing of triglyceride-rich lipoproteins (TRLs) by inhibiting LPL, but that view is based largely on studies of free LPL. We now recognize that intravascular LPL is neither free nor loosely bound, but instead is tightly bound to glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GPIHBP1) on endothelial cells. Here, we revisited the effects of apoC-III on LPL, focusing on apoC-IIIŉs capacity to affect the activity of GPIHBP1-bound LPL. We found that TRLs from APOC3 transgenic mice bound normally to GPIHBP1-bound LPL on cultured cells in vitro and to heart capillaries in vivo. However, the triglycerides in apoC-III–enriched TRLs were hydrolyzed more slowly by free LPL, and the inhibitory effect of apoC-III on triglyceride lipolysis was exaggerated when LPL was bound to GPIHBP1 on the surface of agarose beads. Also, recombinant apoC-III reduced triglyceride hydrolysis by free LPL only modestly, but the inhibitory effect was greater when the LPL was bound to GPIHBP1. A mutant apoC-III associated with low plasma triglyceride levels (p.A23T) displayed a reduced capacity to inhibit free and GPIHBP1-bound LPL. Our results show that apoC-III potently inhibits triglyceride hydrolysis when LPL is bound to GPIHBP1.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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