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

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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