Imperial College London
Alternate

DrIainDunlop

Faculty of Engineering, Department of Materials

Reader in Biomaterials and Cell Engineering
 
 
 
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Contact

 

+44 (0)20 7594 6731i.dunlop

 
 
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Location

 

1.02Royal School of MinesSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gonzalez-Carter:2016:10.1111/jne.12392,
author = {Gonzalez-Carter, D and Goode, AE and Fiammengo, R and Dunlop, IE and Dexter, DT and Porter, AE},
doi = {10.1111/jne.12392},
journal = {J Neuroendocrinol},
title = {Inhibition of Leptin-ObR Interaction Does not Prevent Leptin Translocation Across a Human Blood-Brain Barrier Model.},
url = {http://dx.doi.org/10.1111/jne.12392},
volume = {28},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The adipocyte-derived hormone leptin regulates appetite and energy homeostasis through the activation of leptin receptors (ObR) on hypothalamic neurones; hence, leptin must be transported through the blood-brain barrier (BBB) to reach its target sites in the central nervous system. During obesity, however, leptin BBB transport is decreased, in part precluding leptin as a viable clinical therapy against obesity. Although the short isoform of the ObR (ObRa) has been implicated in the transport of leptin across the BBB as a result of its elevated expression in cerebral microvessels, accumulating evidence indicates that leptin BBB transport is independent of ObRa. In the present study, we employed an ObR-neutralising antibody (9F8) to directly examine the involvement of endothelial ObR in leptin transport across an in vitro human BBB model composed of the human endothelial cell line hCMEC/D3. Our results indicate that, although leptin transport across the endothelial monolayer was nonparacellular, and energy- and endocytosis-dependent, it was not inhibited by pre-treatment with 9F8, despite the ability of the latter to recognise hCMEC/D3-expressed ObR, prevent leptin-ObR binding and inhibit leptin-induced signal transducer and activator of transcription 3 (STAT-3) phosphorylation in hCMEC/D3 cells. Furthermore, hCMEC/D3 cells expressed the transporter protein low-density lipoprotein receptor-related protein-2 (LRP-2), which is capable of binding and endocytosing leptin. In conclusion, our results demonstrate that leptin binding to and signalling through ObR is not required for efficient transport across human endothelial monolayers, indicating that ObR is not the primary leptin transporter at the human BBB, a role which may fall upon LRP-2. A deeper understanding of leptin BBB transport will help clarify the exact causes for leptin resistance seen in obesity and aid in the development of more efficient BBB-penetrating leptin analogues.
AU  - Gonzalez-Carter,D
AU  - Goode,AE
AU  - Fiammengo,R
AU  - Dunlop,IE
AU  - Dexter,DT
AU  - Porter,AE
DO  - 10.1111/jne.12392
PY  - 2016///
TI  - Inhibition of Leptin-ObR Interaction Does not Prevent Leptin Translocation Across a Human Blood-Brain Barrier Model.
T2  - J Neuroendocrinol
UR  - http://dx.doi.org/10.1111/jne.12392
UR  - https://www.ncbi.nlm.nih.gov/pubmed/27037668
UR  - http://hdl.handle.net/10044/1/31687
VL  - 28
ER  -
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