Kastin A J, Pan W, Maness L M, Koletsky R J, Ernsberger P
Veterans Affairs Medical Center and Tulane University School of Medicine, New Orleans, LA 70112-1262, USA.
Peptides. 1999 Dec;20(12):1449-53. doi: 10.1016/s0196-9781(99)00156-4.
Leptin is produced in adipose tissue in the periphery, but its satiety effect is exerted in the CNS that it reaches by a saturable transport system across the blood-brain barrier (BBB). The short form of the leptin receptor has been hypothesized to be the transporter, with impaired transport of leptin being implicated in obesity. In Koletsky rats, the splice variant that gives rise to the short form of the leptin receptor contains a point mutation that results in marked obesity. We studied the transport of leptin across the BBB in Koletsky rats and found it to be significantly less than in their lean littermates. By contrast, Sprague-Dawley rats matched in weight to each of these two groups showed no difference in the blood-to-brain influx of leptin. HPLC showed that most of the leptin crossing the BBB in rats remained intact and capillary depletion showed that most of the leptin reached the parenchyma of the brain. The results indicate that the short form of the leptin receptor is involved in the transport of leptin across the BBB.
瘦素在外周脂肪组织中产生，但其饱腹感效应在中枢神经系统中发挥作用，它通过一种可饱和的转运系统穿过血脑屏障（BBB）到达中枢神经系统。瘦素受体的短形式被认为是转运体，瘦素转运受损与肥胖有关。在科列茨基大鼠中，产生瘦素受体短形式的剪接变体包含一个点突变，导致明显肥胖。我们研究了瘦素在科列茨基大鼠血脑屏障中的转运，发现其转运量明显低于其瘦的同窝大鼠。相比之下，体重与这两组大鼠匹配的斯普拉格-道利大鼠在瘦素的血脑内流方面没有差异。高效液相色谱法显示，穿过大鼠血脑屏障的瘦素大部分保持完整，毛细血管耗竭显示大部分瘦素到达脑实质。结果表明，瘦素受体的短形式参与了瘦素穿过血脑屏障的转运。
