RT Journal Article T1 Is LRP2 Involved in Leptin Transport over the Blood-Brain Barrier and Development of Obesity? A1 Sandin, Elvira S. A1 Folberth, Julica A1 Müller-Fielitz, Helge A1 Pietrzik, Claus Ulrich A1 Herold, Elisabeth A1 Willnow, Thomas A1 Pfluger, Paul A1 Nogueiras Pozo, Rubén A1 Prevot, Vincent A1 Krey, Thomas A1 Schwaninger, Markus K1 Leptin K1 Blood-brain barrier K1 LRP2 K1 ERK1/2 K1 Gaussia luciferase K1 Fusion protein AB 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 PB MDPI YR 2021 FD 2021 LK http://hdl.handle.net/10347/26250 UL http://hdl.handle.net/10347/26250 LA eng NO Int. J. Mol. Sci. 2021, 22(9), 4998; https://doi.org/10.3390/ijms22094998 NO This project has received funding from the Deutsche Forschungsgemeinschaft (GRK1957) to M.S. and the European Research Council (ERC) Synergy Grant-2019-WATCH-810331 to V.P., R.N. and M.S. DS Minerva RD 4 may 2026