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 9

Confocal micrographs demonstrating GPIHBP1 and LPL on the luminal surface of SFO capillaries and median eminence (ME) capillaries in WT mice but not Gpihbp1–/– mice.

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Confocal micrographs demonstrating GPIHBP1 and LPL on the luminal surfac...
Gpihbp1–/– mice and littermate WT mice were given an IV injection of Alexa Fluor 555–11A12 (against GPIHBP1), Alexa Fluor 647–27A7 (against mouse LPL), and Alexa Fluor 488–MECA-32 (against PLVAP). After 2 min, the vasculature was perfused with PBS and PFA, and tissue sections were prepared for microscopy. In A, GPIHBP1 is green; LPL is purple, and PLVAP is red. In B, GPIHBP1 is purple, LPL is green, and PLVAP is red. Shown in A are representative images from SFO capillaries (n = 3 independent experiments). Shown in B are representative images from ME capillaries (n = 2 independent experiments). C shows a control experiment documenting effective vascular perfusion of the ME. In this experiment, mice were given an IV injection of Alexa Fluor 647–Ab27A7 (against LPL; green) and Alexa Fluor 555–nonimmune goat IgG (purple). After 2 min, the vasculature was perfused with PBS and PFA; tissue sections were stained with mAb MECA-32 followed by Alexa Fluor 488–anti-rat IgG (H+L) (red). The absence of goat IgG in the capillary lumen indicates that the vasculature had been effectively perfused. All images in this figure were recorded with a 20 × objective. Scale bars: 50 μm. 3V, third ventricle.