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Sandin, E.S.* ; Folberth, J.* ; Müller-Fielitz, H.* ; Pietrzik, C.U.* ; Herold, E.* ; Willnow, T.E.* ; Pfluger, P.T. ; Nogueiras, R.* ; Prévot, V.* ; Schwaninger, M.*

Is LRP2 involved in leptin transport over the blood-brain barrier and development of obesity?

Int. J. Mol. Sci. 22:4998 (2021)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The mechanisms underlying the transport of leptin into the brain are still largely unclear. While the leptin receptor has been implicated in the transport process, recent evidence has suggested an additional role of LRP2 (megalin). To evaluate the function of LRP2 for leptin transport across the blood-brain barrier (BBB), we developed a novel leptin-luciferase fusion protein (pLG), which stimulated leptin signaling and was transported in an in vitro BBB model based on porcine endothelial cells. The LRP inhibitor RAP did not affect leptin transport, arguing against a role of LRP2. In line with this, the selective deletion of LRP2 in brain endothelial cells and epithelial cells of the choroid plexus did not influence bodyweight, body composition, food intake, or energy expenditure of mice. These findings suggest that LRP2 at the BBB is not involved in the transport of leptin into the brain, nor in the development of obesity as has previously been described.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Blood-brain Barrier ; Erk1/2 ; Fusion Protein ; Gaussia Luciferase ; Leptin ; Lrp2; Megalin; Receptor; Mice; Resistance; Stat3; Food; Microvessels; Endocytosis; Phenotype; Tanycytes
ISSN (print) / ISBN 1422-0067
e-ISSN 1661-6596
Zeitschrift International Journal of Molecular Sciences
Quellenangaben Band: 22, Heft: 9, Seiten: , Artikelnummer: 4998 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Förderungen European Research Council (ERC)
Deutsche Forschungsgemeinschaft