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Is LRP2 Involved in Leptin Transport over the Blood-Brain Barrier and Development of Obesity?
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 May 08; Vol. 22 (9). Date of Electronic Publication: 2021 May 08. - Publication Year :
- 2021
-
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.
- Subjects :
- Animals
Binding Sites
Body Composition
Body Weight
CHO Cells
Choroid Plexus metabolism
Cricetulus
Endothelial Cells metabolism
Extracellular Signal-Regulated MAP Kinases metabolism
Female
Luciferases metabolism
Male
Models, Biological
Phosphorylation
Protein Transport
Receptors, Leptin metabolism
Recombinant Fusion Proteins metabolism
Swine
Blood-Brain Barrier metabolism
Leptin metabolism
Low Density Lipoprotein Receptor-Related Protein-2 metabolism
Obesity metabolism
Obesity pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34066779
- Full Text :
- https://doi.org/10.3390/ijms22094998