GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients.
Xuchen HuKen MatsumotoRachel S JungThomas A WestonPatrick J HeizerCuiwen HeNorma P SandovalChristopher M AllanYiping TuHarry V VintersLinda M LiauRochelle M EllisonJazmin E MoralesLynn J BaufeldNicholas A BayleyLiqun HeChrister BetsholtzAnne P BeigneuxDavid A NathansonHolger GerhardtStephen G YoungLoren G FongHaibo JiangPublished in: eLife (2019)
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.
Keyphrases
- endothelial cells
- high grade
- heavy metals
- poor prognosis
- induced apoptosis
- binding protein
- high resolution
- fatty acid
- gene expression
- multiple sclerosis
- cell cycle arrest
- coronary artery
- adipose tissue
- long non coding rna
- blood pressure
- signaling pathway
- photodynamic therapy
- brain injury
- high glucose
- fluorescence imaging
- weight loss
- protein protein
- vascular endothelial growth factor