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GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

Authors

  • X. Hu
  • K. Matsumoto
  • R.S. Jung
  • T.A. Weston
  • P.J. Heizer
  • C. He
  • N.P. Sandoval
  • C.M. Allan
  • Y. Tu
  • H.V. Vinters
  • L.M. Liau
  • R.M. Ellison
  • J.E. Morales
  • L.J. Baufeld
  • N.A. Bayley
  • L. He
  • C. Betsholtz
  • A.P. Beigneux
  • D.A. Nathanson
  • H. Gerhardt
  • S.G. Young
  • L.G. Fong
  • H. Jiang

Journal

  • eLife

Citation

  • Elife 8: e47178

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.


DOI

doi:10.7554/eLife.47178