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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-02-01
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| Series: | Molecular Metabolism |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877817308621 |
| _version_ | 1818968818237571072 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Alessandro Di Spiezio |
| collection | DOAJ |
| description | 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 blood–brain and blood–CSF 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. Keywords: Leptin, Reward, Blood–brain barrier, LepR, Obesity, Endothelial cells |
| first_indexed | 2024-12-20T14:10:44Z |
| format | Article |
| id | doaj.art-f16f2cfd419748e59d456e48e28cc416 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-20T14:10:44Z |
| publishDate | 2018-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-f16f2cfd419748e59d456e48e28cc4162022-12-21T19:38:09ZengElsevierMolecular Metabolism2212-87782018-02-0181322The LepR-mediated leptin transport across brain barriers controls food rewardAlessandro Di Spiezio0Elvira Sonia Sandin1Riccardo Dore2Helge Müller-Fielitz3Steffen E. Storck4Mareike Bernau5Walter Mier6Henrik Oster7Olaf Jöhren8Claus U. Pietrzik9Hendrik Lehnert10Markus Schwaninger11Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, GermanyInstitute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, GermanyDepartment of Internal Medicine, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, GermanyInstitute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, GermanyInstitute for Pathobiochemistry, University Medical Center, Johannes Gutenberg University of Mainz, Duesbergweg 6, 55099 Mainz, GermanyInstitute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, GermanyDepartment of Radiochemistry, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, GermanyInstitute of Neurobiology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, GermanyCenter of Brain, Behavior and Metabolism, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, GermanyInstitute for Pathobiochemistry, University Medical Center, Johannes Gutenberg University of Mainz, Duesbergweg 6, 55099 Mainz, GermanyDepartment of Internal Medicine, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany; Deutsches Zentrum für Diabetesforschung, Ratzeburger Allee 160, 23562 Lübeck, GermanyInstitute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany; Corresponding author.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 blood–brain and blood–CSF 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. Keywords: Leptin, Reward, Blood–brain barrier, LepR, Obesity, Endothelial cellshttp://www.sciencedirect.com/science/article/pii/S2212877817308621 |
| spellingShingle | 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 The LepR-mediated leptin transport across brain barriers controls food reward Molecular Metabolism |
| title | The LepR-mediated leptin transport across brain barriers controls food reward |
| title_full | The LepR-mediated leptin transport across brain barriers controls food reward |
| title_fullStr | The LepR-mediated leptin transport across brain barriers controls food reward |
| title_full_unstemmed | The LepR-mediated leptin transport across brain barriers controls food reward |
| title_short | The LepR-mediated leptin transport across brain barriers controls food reward |
| title_sort | lepr mediated leptin transport across brain barriers controls food reward |
| url | http://www.sciencedirect.com/science/article/pii/S2212877817308621 |
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