GPIHBP1, lipoprotein lipase, and triglyceride-rich lipoproteins in capillaries of the choroid plexus and circumventricular organs
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
- Lee S. Nguyen (ORCID: https://orcid.org/0000-0002-6014-6269)
- Liqun He (ORCID: https://orcid.org/0000-0003-2127-7597)
- Yiping Tu (ORCID: https://orcid.org/0000-0002-4630-9113)
- Wenxin Song (ORCID: https://orcid.org/0000-0002-6568-4461)
- Shino Magaki (ORCID: https://orcid.org/0000-0003-0433-5759)
- Ye Yang (ORCID: https://orcid.org/0000-0003-4260-7700)
- Ellen Kozlov
- Christopher Kazu Williams (ORCID: https://orcid.org/0000-0003-3253-7630)
- Maarja Andaloussi Mäe (ORCID: https://orcid.org/0000-0001-6985-4379)
- T. Lowe
- Joonyoung R. Kim (ORCID: https://orcid.org/0009-0009-1276-6971)
- Christer Betsholtz (ORCID: https://orcid.org/0000-0002-8494-971X)
- Hyesoo Jung (ORCID: https://orcid.org/0000-0002-6343-4338)
- Loren G. Fong (ORCID: https://orcid.org/0000-0002-4465-5290)
- Michael Ploug (ORCID: https://orcid.org/0000-0003-2215-4265)
- Haibo Jiang (ORCID: https://orcid.org/0000-0002-2384-4826)
- M. Hung
- Stephen G. Young (ORCID: https://orcid.org/0000-0001-7270-3176)
- Jenna P Koerner
- Anne P. Beigneux (ORCID: https://orcid.org/0000-0002-7892-150X)
- Ashley Presnell
- Julia Scheithauer
- Paul Kim (ORCID: https://orcid.org/0000-0002-1755-6182)
- Anh P. Tran
- James Carroll
Institutions
- Uppsala University (SE)
- University of Copenhagen (DK)
- University of California, Los Angeles (US)
- Copenhagen University Hospital (DK)
- Karolinska Institutet (SE)
- Integrated Cardio Metabolic Centre (SE)
- University of Hong Kong (HK)
Publication Details
- Journal
- Journal of Clinical Investigation
- Published
- 2025-09-30
- DOI
- https://doi.org/10.1172/jci191867
- Citations
- 1
- Primary Topic
- Lipid metabolism and disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.39