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Is LRP2 involved in leptin transport over the blood-brain barrier and development of obesity?
Int. J. Mol. Sci. 22:4998 (2021)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
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
Quellenangaben
Volume: 22,
Issue: 9,
Article Number: 4998
Publisher
MDPI
Publishing Place
Basel
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)
Grants
European Research Council (ERC)
Deutsche Forschungsgemeinschaft
Deutsche Forschungsgemeinschaft