GPIHBP1, lipoprotein lipase, and triglyceride-rich lipoproteins in capillaries of the choroid plexus and circumventricular organs
Wenxin Song, … , Loren G. Fong, Stephen G. Young
Wenxin Song, … , Loren G. Fong, Stephen G. Young
Published October 1, 2025
Citation Information: J Clin Invest. 2025;135(19):e191867. https://doi.org/10.1172/JCI191867.
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Research Article Metabolism Vascular biology

GPIHBP1, lipoprotein lipase, and triglyceride-rich lipoproteins in capillaries of the choroid plexus and circumventricular organs

Abstract

In peripheral tissues, an endothelial cell (EC) protein, GPIHBP1, captures lipoprotein lipase (LPL) from the interstitial spaces and transports it to the capillary lumen. LPL mediates the margination of triglyceride-rich (TG-rich) lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. TRL-derived fatty acids are used for fuel in oxidative tissues or stored in adipose tissue. In mice, GPIHBP1 is absent from capillary ECs of the brain (which uses glucose for fuel); consequently, LPL and TRL margination are absent in mouse brain capillaries. However, because fatty acids were reported to play signaling roles in the brain, we hypothesized that LPL-mediated TRL processing might occur within specialized vascular beds within the central nervous system. Here, we show that GPIHBP1 is expressed in capillary ECs of human and mouse choroid plexus (ChP) and that GPIHBP1 transports LPL (produced by adjacent ChP cells) to the capillary lumen. The LPL in ChP capillaries mediates both TRL margination and processing. Intracapillary LPL and TRL margination are absent in the ChP of Gpihbp1–/– mice. GPIHBP1 expression, intracapillary LPL, and TRL margination were also observed in the median eminence and subfornical organ, circumventricular organs implicated in the regulation of food intake.

Authors

Wenxin Song, Madison Hung, Ellen Kozlov, Megan Hung, Anh P. Tran, James Carroll, Le Phoung Nguyen, Troy L. Lowe, Paul Kim, Hyesoo Jung, Yiping Tu, Joonyoung Kim, Ashley M. Presnell, Julia Scheithauer, Jenna P. Koerner, Ye Yang, Shino D. Magaki, Christopher K. Williams, Michael Ploug, Haibo Jiang, Christer Betsholtz, Maarja Andaloussi Mäe, Liqun He, Anne P. Beigneux, Loren G. Fong, Stephen G. Young

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Figure 2

GPIHBP1 and LPL are on the luminal surface of ChP capillaries in WT mice but not Gpihbp1–/– mice.

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GPIHBP1 and LPL are on the luminal surface of ChP capillaries in WT mice...
(A) Confocal micrographs of the ChP. Alexa Fluor 488–MECA-32 (against plasmalemma vesicle-associated protein [PLVAP]; green), Alexa Fluor 555–11A12 (against GPIHBP1; red), and Alexa Fluor 647–27A7 (against LPL; white) were injected IV into WT mice. After 2 min, the vasculature was perfused extensively with PBS and PFA, and tissue sections were prepared for microscopy. DNA was stained with DAPI. mAbs 11A12 and 27A7 bound to the luminal surface of PLVAP-positive ChP capillaries. Scale bar: 50 μm. (B and C) Confocal micrographs to assess binding of 11A12 and 27A7 to the luminal surface of ChP capillaries in WT and Gpihbp1–/– mice. Mice were given an IV injection of Alexa Fluor 647–27A7 (white), Alexa Fluor 555–11A12 (red), and Alexa Fluor 488–wheat germ agglutinin (WGA, green). After 2 min, the vasculature was perfused, and tissue sections were prepared for microscopy. In C, ChP epithelial cells were identified with an AQP-1–specific mAb followed by Alexa Fluor Plus 405–anti-rabbit IgG (H+L) (purple). GPIHBP1 and LPL were detected along the luminal surface of ChP capillaries in WT mice (white arrows) but not in Gpihbp1–/– mice. WGA bound to capillaries in the ChP and the brain parenchyma (purple arrows). Boxed images of the ChP in C are shown below at higher magnification. Images were recorded with a 20 objective. Scale bar, 50 μm.