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

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Item Type:Article
Title:Is LRP2 involved in leptin transport over the blood-brain barrier and development of obesity?
Creators Name:Sandin, E.S. and Folberth, J. and Müller-Fielitz, H. and Pietrzik, C.U. and Herold, E. and Willnow, T.E. and Pfluger, P.T. and Nogueiras, R. and Prevot, V. and Krey, T. and Schwaninger, M.
Abstract: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.
Keywords:Leptin, Blood-Brain Barrier, LRP2, ERK1/2, Gaussia Luciferase, Fusion Protein, Animals, Cricetulus, Swine
Source:International Journal of Molecular Sciences
ISSN:1422-0067
Publisher:MDPI
Volume:22
Number:9
Page Range:4998
Date:8 May 2021
Official Publication:https://doi.org/10.3390/ijms22094998
PubMed:View item in PubMed

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