Partial saturation and regional variation in the blood-to-brain transport of leptin in normal weight mice
Partial saturation and regional variation in the blood-to-brain transport of leptin in normal weight mice
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DOI：
10.1152/ajpendo.2000.278.6.e1158
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发表时间：
2000-06-01
影响因子：
5.1
通讯作者：
Farrell, CL
中科院分区：
文献类型：
--
作者：
Banks, WA;Clever, CM;Farrell, CL
瘦素进入弓状核的血脑屏障转运受损已被认为是人类和远交老化小鼠肥胖的基础。在这里，我们使用了小鼠脑灌注方法来测量血管浓度在0.15和130 ng/ml之间的瘦素的运输速率和动力学参数。运输到整个大脑部分饱和在所有浓度，不仅是那些肥胖。瘦素进入大脑的所有区域，而不仅仅是下丘脑，进入和饱和率在大脑区域之间存在差异。该转运蛋白的米氏常数的值接近正常血清水平，并且最大速度值在脑区域之间变化显著。这些结果表明低血清水平向大脑发出饥饿状态信号的重要作用，并表明肥胖症中观察到的瘦素水平极大地饱和了转运蛋白。区域摄取和饱和度的差异提供了一种机制，通过该机制瘦素可以控制在弓状核和中枢神经系统的其他区域介导的事件，具有不同的区域阈值以实现最佳功能。
Impaired blood-brain barrier transport of leptin into the arcuate nucleus has been suggested to underlie obesity in humans and outbred aging mice. Here, we used a brain perfusion method in mice to measure transport rates and kinetic parameters for leptin at vascular concentrations between 0.15 and 130 ng/ml. Transport into whole brain was partially saturated at all concentrations, not only those seen in obesity. Leptin entered all regions of the brain, not only the hypothalamus, with entry and saturation rates differing among the brain regions. The value of the Michaelis-Menten constant of the transporter approximates normal serum levels and the maximum velocity value varies significantly among brain regions. These results suggest an important role for low serum levels signaling starvation status to the brain and show that the levels of leptin seen in obesity greatly saturate the transporter. Differences in regional uptake and saturation provide a mechanism by which leptin can control events mediated at the arcuate nucleus and other regions of the central nervous system with different regional thresholds for optimal function.