GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

Xuchen Hu, Ken Matsumoto, Rachel S. Jung, Thomas A. Weston, Patrick J. Heizer, Cuiwen He, Norma P. Sandoval, Christopher M. Allan, Yiping Tu, Harry V. Vinters, Linda M. Liau, Rochelle M. Ellison, Jazmin E. Morales, Lynn J. Baufeld, Nicholas A. Bayley, Liqun He, Christer Betsholtz, Anne P. Beigneux, David A. Nathanson, Holger Gerhardt & 3 others Stephen G. Young, Loren G. Fong, Haibo Jiang

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Article numbere47178
Number of pages29
JournaleLife
Volume8
DOIs
Publication statusPublished - 6 Jun 2019

Cite this

Hu, X., Matsumoto, K., Jung, R. S., Weston, T. A., Heizer, P. J., He, C., ... Jiang, H. (2019). GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients. eLife, 8, [e47178]. https://doi.org/10.7554/eLife.47178
Hu, Xuchen ; Matsumoto, Ken ; Jung, Rachel S. ; Weston, Thomas A. ; Heizer, Patrick J. ; He, Cuiwen ; Sandoval, Norma P. ; Allan, Christopher M. ; Tu, Yiping ; Vinters, Harry V. ; Liau, Linda M. ; Ellison, Rochelle M. ; Morales, Jazmin E. ; Baufeld, Lynn J. ; Bayley, Nicholas A. ; He, Liqun ; Betsholtz, Christer ; Beigneux, Anne P. ; Nathanson, David A. ; Gerhardt, Holger ; Young, Stephen G. ; Fong, Loren G. ; Jiang, Haibo. / GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients. In: eLife. 2019 ; Vol. 8.
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title = "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.",
keywords = "biochemistry, cancer metabolism, chemical biology, endothelial cells, human, human biology, lipolysis, lipoprotein lipase, medicine, mouse, NanoSIMS, triglycerides",
author = "Xuchen Hu and Ken Matsumoto and Jung, {Rachel S.} and Weston, {Thomas A.} and Heizer, {Patrick J.} and Cuiwen He and Sandoval, {Norma P.} and Allan, {Christopher M.} and Yiping Tu and Vinters, {Harry V.} and Liau, {Linda M.} and Ellison, {Rochelle M.} and Morales, {Jazmin E.} and Baufeld, {Lynn J.} and Bayley, {Nicholas A.} and Liqun He and Christer Betsholtz and Beigneux, {Anne P.} and Nathanson, {David A.} and Holger Gerhardt and Young, {Stephen G.} and Fong, {Loren G.} and Haibo Jiang",
year = "2019",
month = "6",
day = "6",
doi = "10.7554/eLife.47178",
language = "English",
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issn = "2050-084X",
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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 & Jiang, H 2019, 'GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients' eLife, vol. 8, e47178. https://doi.org/10.7554/eLife.47178

GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients. / Hu, Xuchen; Matsumoto, Ken; Jung, Rachel S.; Weston, Thomas A.; Heizer, Patrick J.; He, Cuiwen; Sandoval, Norma P.; Allan, Christopher M.; Tu, Yiping; Vinters, Harry V.; Liau, Linda M.; Ellison, Rochelle M.; Morales, Jazmin E.; Baufeld, Lynn J.; Bayley, Nicholas A.; He, Liqun; Betsholtz, Christer; Beigneux, Anne P.; Nathanson, David A.; Gerhardt, Holger; Young, Stephen G.; Fong, Loren G.; Jiang, Haibo.

In: eLife, Vol. 8, e47178, 06.06.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

AU - Hu, Xuchen

AU - Matsumoto, Ken

AU - Jung, Rachel S.

AU - Weston, Thomas A.

AU - Heizer, Patrick J.

AU - He, Cuiwen

AU - Sandoval, Norma P.

AU - Allan, Christopher M.

AU - Tu, Yiping

AU - Vinters, Harry V.

AU - Liau, Linda M.

AU - Ellison, Rochelle M.

AU - Morales, Jazmin E.

AU - Baufeld, Lynn J.

AU - Bayley, Nicholas A.

AU - He, Liqun

AU - Betsholtz, Christer

AU - Beigneux, Anne P.

AU - Nathanson, David A.

AU - Gerhardt, Holger

AU - Young, Stephen G.

AU - Fong, Loren G.

AU - Jiang, Haibo

PY - 2019/6/6

Y1 - 2019/6/6

N2 - 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.

AB - 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.

KW - biochemistry

KW - cancer metabolism

KW - chemical biology

KW - endothelial cells

KW - human

KW - human biology

KW - lipolysis

KW - lipoprotein lipase

KW - medicine

KW - mouse

KW - NanoSIMS

KW - triglycerides

UR - http://www.scopus.com/inward/record.url?scp=85068887058&partnerID=8YFLogxK

U2 - 10.7554/eLife.47178

DO - 10.7554/eLife.47178

M3 - Article

VL - 8

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e47178

ER -

Hu X, Matsumoto K, Jung RS, Weston TA, Heizer PJ, He C et al. GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients. eLife. 2019 Jun 6;8. e47178. https://doi.org/10.7554/eLife.47178