Elsevier

Molecular Metabolism

Volume 8, February 2018, Pages 13-22
Molecular Metabolism

Original Article
The LepR-mediated leptin transport across brain barriers controls food reward

https://doi.org/10.1016/j.molmet.2017.12.001Get rights and content
Under a Creative Commons license
open access

Highlights

  • LepR mediates the transport of leptin across brain barriers.

  • The LepR-mediated transport of leptin across brain barriers modulates food reward.

  • The homeostatic feeding control does not depend on LepR-mediated leptin transport.

Abstract

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

Abbreviations

ARC
arcuate nucleus
BBB
blood–brain barrier
BC
bottle choice test
BSA
bovine serum albumin
CPP
conditioned place preference
CSF
cerebrospinal fluid
DAPI
4′,6-diamidino-2-phenylindole
HFD
high-fat diet
i.p.
intraperitoneal
LepR
leptin receptor
NCD
normal chow diet
PBS
phosphate buffered saline
PFA
paraformaldehyde
qPCR
quantitative polymerase chain reaction
VTA
ventral tegmental area

Cited by (0)