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

Elvira S. Sandin, Julica Folberth, Helge Müller-Fielitz, Claus U. Pietrzik, Elisabeth Herold, Thomas E. Willnow, Paul T. Pfluger, Ruben Nogueiras, Vincent Prevot, Thomas Krey, Markus Schwaninger*

*Corresponding author for this work


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.

Original languageEnglish
Article number4998
JournalInternational Journal of Molecular Sciences
Issue number9
Publication statusPublished - 01.05.2021

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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