The LepR-mediated leptin transport across brain barriers controls food reward
Objective: Leptin is a key hormone in the control of appetite and body weight. Predominantly produced by white adipose tissue, it acts on the brain to inhibit homeostatic feeding and food reward. Leptin has free access to circumventricular organs, such as the median eminence, but entry into other br...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 2018
|
| In: |
Molecular metabolism
Year: 2018, Volume: 8, Pages: 13-22 |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2017.12.001 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.molmet.2017.12.001 Verlag, Volltext: https://linkinghub.elsevier.com/retrieve/pii/S2212877817308621 
|
| Author Notes: | Alessandro Di Spiezio, Elvira Sonia Sandin, Riccardo Dore, Helge Müller-Fielitz, Steffen E. Storck, Mareike Bernau, Walter Mier, Henrik Oster, Olaf Jöhren, Claus U. Pietrzik, Hendrik Lehnert, Markus Schwaninger |
| Summary: | Objective: Leptin is a key hormone in the control of appetite and body weight. Predominantly produced by white adipose tissue, it acts on the brain to inhibit homeostatic feeding and food reward. Leptin has free access to circumventricular organs, such as the median eminence, but entry into other brain centers is restricted by the bloodebrain and bloodeCSF barriers. So far, it is unknown for which of its central effects leptin has to penetrate brain barriers. In addition, the mechanisms mediating the transport across barriers are unclear although high expression in brain barriers suggests an important role of the leptin receptor (LepR).Methods: We selectively deleted LepR in brain endothelial and epithelial cells of mice (LepRbeKO). The expression of LepR in fenestrated vessels of the periphery and the median eminence as well as in tanycytes was not affected.Results: Perfusion studies showed that leptin uptake by the brain depended on LepR in brain barriers. When being fed with a rewarding high-fat diet LepRbeKO mice gained more body weight than controls. The aggravated obesity of LepRbeKO mice was due to hyperphagia and a higher sensitivity to food reward.Conclusions: The LepR-mediated transport of leptin across brain barriers in endothelial cells lining microvessels and in epithelial cells of the choroid plexus controls food reward but is apparently not involved in homeostatic control of feeding. Ó 2017 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
|---|---|
| Item Description: | Available online 7 December 2017 Gesehen am 08.11.2018 |
| Physical Description: | Online Resource |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2017.12.001 |