OSCR

GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain.

Overview

Authors: Minjun Liu1, Madison Hung1, Ellen Kozlov1, Megan Hung1, Mariana Colaço-Gaspar1, Shristi Roy1, Yiping Tu1, Shino D Magaki2, Christopher K Williams2, Maarja Andaloussi Mäe3, Erik C B Johnson4, Robert W Siegel5, Robert J Konrad5, Michael Ploug6,7, Christer Betsholtz3,8, Anne P Beigneux1, Liqun He3, Loren G Fong1, Stephen G Young1,9
  1. Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
  2. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
  3. Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala 75185, Sweden
  4. Department of Neurology, Emory University, Atlanta, GE 30329
  5. Laboratory for Experimental Medicine, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46225
  6. Finsen Laboratory Copenhagen University Hospital–Rigshospitalet, Copenhagen N DK-2200, Denmark
  7. Biotechnology Research and Innovation Centre, University of Copenhagen, Copenhagen N DK-2200, Denmark
  8. Department of Medicine-Huddinge, Karolinska Institute Campus Flemingsberg, Huddinge SE-141 83, Sweden
  9. Department of Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095
Institutions: University of California, Los Angeles (United States); Uppsala University (Sweden); Emory University (United States); Eli Lilly (United States) (United States); University of Copenhagen (Denmark); Copenhagen University Hospital (Denmark); Rigshospitalet (Denmark); Karolinska Institutet (Sweden)
Dates: received 25 March 2026; accepted 5 May 2026; published online 1 June 2026; in print 9 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1073/pnas.2610646123 · PMID 42224591 · PMCID PMC13250511 · OpenAlex W7163025137
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: histology / microscopy (modality), human (organism), cellular / molecular (subfield)
Methods: Smoothing, state filtering, decompositions, Machine learning
Keywords: GPIHBP1, lipoprotein lipase, oligodendrocyte, myelin
MeSH: Brain*, Lipoprotein Lipase*, Oligodendroglia*, Receptors, Lipoprotein*, Animals, Humans, Protein Binding (* major topic)
Topic: Lipid metabolism and disorders (Cardiology and Cardiovascular Medicine, Medicine), according to OpenAlex
Funding: HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) (HL171737 HL087228 HL176438 HL139725); NHLBI NIH HHS (R01 HL171737, R01 HL087228); Leducq Foundation (23CVD02); The John and Birthe Meyer Foundation (000); Swedish Research Council (2023-02655, 2015-00550)
Citations: not cited yet (Europe PMC); 85 references in the paper

Abstract

In peripheral tissues, lipoprotein lipase (LPL) is secreted by parenchymal cells (adipocytes, myocytes) into the interstitial spaces, where it is captured by GPIHBP1 (a glycosylphosphatidylinositol-anchored protein of capillary endothelial cells) and escorted to the luminal surface of capillaries. The LPL inside capillaries hydrolyzes glycerolipids in the plasma lipoproteins, releasing fatty acids for parenchymal cells. In the central nervous system, LPL is synthesized by multiple cell types [e.g., microglia, oligodendrocyte precursor cells (OPCs)] and secreted into the interstitium, but a binding site for the LPL has never been identified. By examining single nuclei RNA-seq databases of the human brain, we found that GPIHBP1 is expressed by oligodendrocytes but not by OPCs. This gene-expression profile (high in oligodendrocytes, low in OPCs) is also observed in genes for myelin structural proteins, fatty acid binding and transport proteins, and lipid biosynthetic enzymes. GPIHBP1 expression in oligodendrocytes was confirmed by in situ hybridization studies of human brain and by immunohistochemical staining. Of note, GPIHBP1 and LPL are colocalized on oligodendrocytes in the human brain. Our findings identify GPIHBP1 as a principal binding site for interstitial LPL in the human brain and suggest that GPIHBP1-bound LPL could hydrolyze interstitial lipids and thereby supply oligodendrocytes with fatty acid nutrients.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data, Materials, and Software Availability

Study data are included in the article and/or SI Appendix (http://www.pnas.org/lookup/doi/10.1073/pnas.2610646123#supplementary-materials).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 19 authors, 4 keywords, 7 MeSH terms, 5 funders, 85 references.

Cite

This paper

Liu, M., Hung, M., Kozlov, E., Hung, M., Colaço-Gaspar, M., Roy, S., Tu, Y., Magaki, S. D., Williams, C. K., Andaloussi Mäe, M., Johnson, E. C. B., Siegel, R. W., Konrad, R. J., Ploug, M., Betsholtz, C., Beigneux, A. P., He, L., Fong, L. G., & Young, S. G. (2026). GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain. Proceedings of the National Academy of Sciences of the United States of America, 123(23), e2610646123. https://doi.org/10.1073/pnas.2610646123

BibTeX

@article{liu2026gpihbp1,
author = {Liu, Minjun and Hung, Madison and Kozlov, Ellen and Hung, Megan and Colaço-Gaspar, Mariana and Roy, Shristi and Tu, Yiping and Magaki, Shino D and Williams, Christopher K and Andaloussi Mäe, Maarja and Johnson, Erik C B and Siegel, Robert W and Konrad, Robert J and Ploug, Michael and Betsholtz, Christer and Beigneux, Anne P and He, Liqun and Fong, Loren G and Young, Stephen G},
title = {{GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = jun,
volume = {123},
number = {23},
pages = {e2610646123},
publisher = {National Academy of Sciences},
issn = {0027-8424},
doi = {10.1073/pnas.2610646123},
url = {https://doi.org/10.1073/pnas.2610646123},
pmid = {42224591},
pmcid = {PMC13250511}
}

RIS

TY - JOUR
AU - Liu, Minjun
AU - Hung, Madison
AU - Kozlov, Ellen
AU - Hung, Megan
AU - Colaço-Gaspar, Mariana
AU - Roy, Shristi
AU - Tu, Yiping
AU - Magaki, Shino D
AU - Williams, Christopher K
AU - Andaloussi Mäe, Maarja
AU - Johnson, Erik C B
AU - Siegel, Robert W
AU - Konrad, Robert J
AU - Ploug, Michael
AU - Betsholtz, Christer
AU - Beigneux, Anne P
AU - He, Liqun
AU - Fong, Loren G
AU - Young, Stephen G
TI - GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain
T2 - Proceedings of the National Academy of Sciences of the United States of America
J2 - Proc Natl Acad Sci U S A
PY - 2026
DA - 2026/06/01
VL - 123
IS - 23
SP - e2610646123
SN - 0027-8424
PB - National Academy of Sciences
DO - 10.1073/pnas.2610646123
UR - https://doi.org/10.1073/pnas.2610646123
LA - en
ER -

CSL-JSON

{
"id": "10.1073/pnas.2610646123",
"type": "article-journal",
"title": "GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain",
"container-title": "Proceedings of the National Academy of Sciences of the United States of America",
"author": [
{
"family": "Liu",
"given": "Minjun"
},
{
"family": "Hung",
"given": "Madison"
},
{
"family": "Kozlov",
"given": "Ellen"
},
{
"family": "Hung",
"given": "Megan"
},
{
"family": "Colaço-Gaspar",
"given": "Mariana"
},
{
"family": "Roy",
"given": "Shristi"
},
{
"family": "Tu",
"given": "Yiping"
},
{
"family": "Magaki",
"given": "Shino D"
},
{
"family": "Williams",
"given": "Christopher K"
},
{
"family": "Andaloussi Mäe",
"given": "Maarja"
},
{
"family": "Johnson",
"given": "Erik C B"
},
{
"family": "Siegel",
"given": "Robert W"
},
{
"family": "Konrad",
"given": "Robert J"
},
{
"family": "Ploug",
"given": "Michael"
},
{
"family": "Betsholtz",
"given": "Christer"
},
{
"family": "Beigneux",
"given": "Anne P"
},
{
"family": "He",
"given": "Liqun"
},
{
"family": "Fong",
"given": "Loren G"
},
{
"family": "Young",
"given": "Stephen G"
}
],
"container-title-short": "Proc Natl Acad Sci U S A",
"volume": "123",
"issue": "23",
"page": "e2610646123",
"DOI": "10.1073/pnas.2610646123",
"PMID": "42224591",
"PMCID": "PMC13250511",
"ISSN": "0027-8424",
"publisher": "National Academy of Sciences",
"URL": "https://doi.org/10.1073/pnas.2610646123",
"language": "en",
"issued": {
"date-parts": [
[
2026,
6,
1
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41467-026-75367-0
Heterogenous microglial reactivity contrasts with stable vascular transcriptional programs in mouse models of Alzheimer's, CADASIL, and Traumatic Brain Injury.
Journal: Nature communications
In common: cellular / molecular, 1 reference, author M A Mäe
[2] doi:10.1093/braincomms/fcag287 [code]
Plasma proteomics reveals molecular overlap between physical activity and dementia risk.
Journal: Brain communications
In common: 2 references
[3] doi:10.1007/s00429-026-03129-1 [code]
Brain structure and function in Homo naledi.
Journal: Brain structure & function
In common: 2 references
[4] doi:10.1186/s12967-026-08266-z [code]
Single-cell multi-omic integration analysis prioritizes druggable genes and reveals cell-type-specific causal effects in glioblastomagenesis.
Journal: Journal of translational medicine
In common: cellular / molecular, 2 references
[5] doi:10.1038/s41467-026-72639-7
Neuregulin-1 facilitates myelin regeneration through microglia-mediated mechanisms in a mouse model of chronic demyelination.
Journal: Nature communications
In common: cellular / molecular, 2 references
[6] doi:10.1038/s41467-026-71803-3 [code]
Charting the transition from in vitro gliogenesis to the in vivo maturation of human glial progenitor cells transplanted into the hypomyelinated mouse brain.
Journal: Nature communications
In common: cellular / molecular, 2 references
[7] doi:10.3389/fbinf.2026.1832826 [code]
Spatial transcriptomics reveal heterogeneous cell‒cell interactions among brain regions in cuprizone model consistent with multiple sclerosis lesions.
Journal: Frontiers in bioinformatics
In common: cellular / molecular, 2 references
[8] doi:10.1038/s41467-026-71643-1 [code]
Pericytes are organ-specific regulators of tissue morphogenesis.
Journal: Nature communications
In common: cellular / molecular, 2 references
[9] doi:10.1126/science.aeb6999
Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis.
Journal: Science (New York, N.Y.)
In common: cellular / molecular, 2 references
[10] doi:10.1038/s41467-026-76676-0 [code]
Determinants of functional burden pleiotropy and gene dosage responses across human traits.
Journal: Nature communications
In common: cellular / molecular, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.