GPIHBP1 Is Responsible for the Entry of Lipoprotein Lipase into Capillaries

The lipolytic processing of triglyceride-rich lipoproteins by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism, providing lipids for storage in adipose tissue and fuel for vital organs such as the heart. LPL is synthesized and secreted by myocytes and adipocytes, but then fin...

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Published in:Cell metabolism 2010-07, Vol.12 (1), p.42-52
Main Authors: Davies, Brandon S.J., Beigneux, Anne P., Barnes, Richard H., Tu, Yiping, Gin, Peter, Weinstein, Michael M., Nobumori, Chika, Nyrén, Rakel, Goldberg, Ira, Olivecrona, Gunilla, Bensadoun, André, Young, Stephen G., Fong, Loren G.
Format: Article
Language:English
Subjects:
Adipose Tissue - blood supply
Animals
Capillaries - enzymology
Endothelial Cells - enzymology
Endothelial Cells - metabolism
HUMDISEASE
Lipid Metabolism
Lipoprotein Lipase - analysis
Lipoprotein Lipase - metabolism
Lipoproteins - metabolism
Mice
Mice, Knockout
Receptors, Lipoprotein - analysis
Receptors, Lipoprotein - genetics
Receptors, Lipoprotein - metabolism
Triglycerides - metabolism
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Summary:The lipolytic processing of triglyceride-rich lipoproteins by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism, providing lipids for storage in adipose tissue and fuel for vital organs such as the heart. LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. The mechanism by which LPL reaches the lumen of capillaries has remained an unresolved problem of plasma lipid metabolism. Here, we show that GPIHBP1 is responsible for the transport of LPL into capillaries. In Gpihbp1-deficient mice, LPL is mislocalized to the interstitial spaces surrounding myocytes and adipocytes. Also, we show that GPIHBP1 is located at the basolateral surface of capillary endothelial cells and actively transports LPL across endothelial cells. Our experiments define the function of GPIHBP1 in triglyceride metabolism and provide a mechanism for the transport of LPL into capillaries. [Display omitted] ► GPIHBP1 is required for proper targeting of LPL to the lumen of capillaries ► GPIHBP1 is found on both the basolateral and apical surfaces of endothelial cells ► GPIHBP1 transports a GPIHBP1-specific monoclonal antibody across endothelial cells ► GPIHBP1 also transports LPL, providing a mechanism for LPL entry into capillaries
ISSN:1550-4131
1932-7420
1932-7420
DOI:10.1016/j.cmet.2010.04.016