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RESEARCH PRODUCT
The LepR-mediated leptin transport across brain barriers controls food reward
Henrik OsterMareike BernauSteffen E. StorckClaus U. PietrzikRiccardo DoreAlessandro Di SpiezioElvira Sonia SandinHendrik LehnertOlaf JöhrenHelge Müller-fielitzWalter MierMarkus Schwaningersubject
Male0301 basic medicineLeptinHFD high-fat dietEndothelial cellsWhite adipose tissueCSF cerebrospinal fluidMice0302 clinical medicineCPP conditioned place preferenceBBB blood–brain barrierCells Culturedmedia_commonLeptindigestive oral and skin physiologyi.p. intraperitonealmedicine.anatomical_structureLepRBlood-Brain BarrierBlood–brain barrier; Endothelial cells; LepR; Leptin; Obesity; RewardMedian eminenceqPCR quantitative polymerase chain reactionReceptors LeptinOriginal ArticleChoroid plexusmedicine.medical_specialtylcsh:Internal medicinemedia_common.quotation_subjectHyperphagiaBiologyBlood–brain barrierVTA ventral tegmental areaBC bottle choice testCapillary PermeabilityBlood–brain barrierARC arcuate nucleus03 medical and health sciencesPBS phosphate buffered salineRewardInternal medicinemedicineAnimalsObesitylcsh:RC31-1245Molecular BiologyCircumventricular organsBlood-Nerve BarrierLeptin receptorNCD normal chow dietAppetiteCell Biology030104 developmental biologyEndocrinologyLepR leptin receptorChoroid PlexusBSA bovine serum albuminPFA paraformaldehyde030217 neurology & neurosurgeryDAPI 4′6-diamidino-2-phenylindoledescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-02-01 | Molecular Metabolism |