Developmental Changes of Leptin Receptors in Cerebral Microvessels: Unexpected Relation to Leptin Transport

Author:

Pan Weihong1,Hsuchou Hung1,Tu Hong1,Kastin Abba J.1

Affiliation:

1. Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808

Abstract

The adipokine leptin participates not only in the regulation of feeding and obesity in adults but also in neonatal development. It crosses the blood-brain barrier (BBB) by receptor-mediated transport. Leptin concentrations in blood differ between neonates and adults. We determined the developmental changes of leptin receptor subtypes in the cerebral microvessels composing the BBB and examined their expected correlation with leptin transport across the BBB. Total RNA was extracted from enriched cerebral microvessels of mice 1, 7, 14, and 60 d of age for real-time RT-PCR analysis of leptin receptor subtypes. In cerebral microvessels from neonates, ObRa, ObRb, ObRc, and ObRe mRNA were all higher than in adults, but ObRd was not detectable. Hypothalamus showed similar age-related changes except for ObRb, which was higher in adults. The homologous receptor gp130 did not show significant age-related changes in either region. Despite the increase of leptin receptors, leptin permeation across the BBB after iv injection was less in the neonates. In situ brain perfusion with blood-free buffer showed no significant difference in the brain uptake of leptin between neonates and adults, indicating an antagonistic role of leptin-binding proteins in the circulation, especially the soluble receptor ObRe. The results are consistent with our previous finding that ObRe antagonizes leptin endocytosis in cultured endothelia and transport from blood to brain in mice. Overall, the developmental changes observed for leptin receptors unexpectedly failed to correlate with the entry of leptin into brain, and this may indicate different functions of the receptors in neonates and adults.

Publisher

The Endocrine Society

Subject

Endocrinology

Cited by 61 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3