GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients.

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. 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 the generation of lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent from the capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in the capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We use NanoSIMS imaging to show 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.

journal_name

Elife

journal_title

eLife

authors

Hu X,Matsumoto K,Jung RS,Weston TA,Heizer PJ,He C,Sandoval NP,Allan CM,Tu Y,Vinters HV,Liau LM,Ellison RM,Morales JE,Baufeld LJ,Bayley NA,He L,Betsholtz C,Beigneux AP,Nathanson DA,Gerhardt H,Young SG,Fong LG,J

doi

10.7554/eLife.47178

subject

Has Abstract

pub_date

2019-06-06 00:00:00

issn

2050-084X

pii

47178

journal_volume

8

pub_type

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