Expression of leptin receptor isoforms in rat brain microvessels
Expression of leptin receptor isoforms in rat brain microvessels
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DOI：
10.1210/en.139.8.3485
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发表时间：
1998-08-01
期刊：
影响因子：
4.8
通讯作者：
Flier, JS
中科院分区：
文献类型：
--
作者：
Bjorbæk, C;Elmquist, JK;Flier, JS
瘦素作用于特定的大脑区域，影响体重调节。由于瘦素是由白色脂肪组织产生的，因此认为瘦素必须穿过血脑屏障或血脑脊髓液屏障才能到达脑内的关键作用部位。已经报道了短型瘦素受体在脉络丛中的高表达。然而，一种或多种已知的瘦素受体亚型是否在脑毛细血管中表达尚不清楚。为了鉴定和定量大鼠脑微血管中的瘦素受体亚型，我们应用定量RT-PCR从纯化的大鼠脑微血管中的RNA与原位杂交平行。结果表明，脑微血管中短型瘦素受体信使RNA（mRNA）含量极高，超过脉络丛。相反，在小脑、下丘脑和脑膜中检测到低水平的这种mRNA。长型瘦素受体mRNA仅以低水平存在于微血管中，但令人惊讶的是，其在小脑中的水平是下丘脑中的5倍。原位杂交实验证实了短瘦素受体在微血管、脉络丛和软脑膜中的强表达。瘦素受体mRNA亚型在脑微血管中的分布和类型与受体介导的瘦素穿过血脑屏障的转运由短瘦素受体亚型介导的可能性一致。
Leptin acts on specific brain regions to affect body weight regulation. As leptin is made by white adipose tissue, it is thought that leptin must cross the blood-brain barrier or the blood-cerebrospinal fluid barrier to reach key sites of action within the brain. High expression of a short form leptin receptor has been reported in the choroid plexus. However, whether one or more of the known leptin receptor isoforms is expressed in brain capillaries is unknown. To identify and quantitate leptin receptor isoforms in rat brain microvessels, we applied quantitative RT-PCR to RNA from purified rat brain microvessels in parallel with in situ hybridization. The results show that the amount of short form leptin receptor messenger RNA (mRNA) in brain microvessels is extremely high, exceeding that in choroid plexus. In contrast, low levels of this mRNA were detected in the cerebellum, hypothalamus, and meninges. The long form leptin receptor mRNA is only present at low levels in the microvessels, but surprisingly, its level in cerebellum is 5 times higher than that in the hypothalamus. In situ hybridization experiments confirmed strong expression of short leptin receptors in microvessels, choroid plexus, and leptomeninges. The distribution and type of leptin receptor mRNA isoforms in brain microvessels are consistent with the possibility that receptor-mediated transport of leptin across the blood-brain barrier is mediated by the short leptin receptor isoform.