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GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

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Item Type:Article
Title:GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients
Creators Name:Hu, X. and Matsumoto, K. and Jung, R.S. and Weston, T.A. and Heizer, P.J. and He, C. and Sandoval, N.P. and Allan, C.M. and Tu, Y. and Vinters, H.V. and Liau, L.M. and Ellison, R.M. and Morales, J.E. and Baufeld, L.J. and Bayley, N.A. and He, L. and Betsholtz, C. and Beigneux, A.P. and Nathanson, D.A. and Gerhardt, H. and Young, S.G. and Fong, L.G. and Jiang, H.
Abstract:GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. The GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for generating lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent in capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We document, by NanoSIMS imaging, that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells.
Keywords:Brain, Capillaries, Carbon Isotopes, Endothelial Cells, Fatty Acids, Glioma, Glucose, Glucose Transporter Type 1, Inbred C57BL Mice, Lipoprotein Lipase, Lipoprotein Receptors, Lipoproteins, Triglycerides, Animals, Mice
Publisher:eLife Sciences Publications
Page Range:e47178
Date:6 June 2019
Official Publication:https://doi.org/10.7554/eLife.47178
PubMed:View item in PubMed

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