Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible
Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible
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DOI：
10.1152/ajpendo.00468.2002
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发表时间：
2003-07-01
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;Farrell, CL
瘦素抵抗是人类肥胖的主要原因。这种抵抗的一个主要组成部分可能是血脑屏障（BBB）中瘦素转运受损。最胖的12月龄正常CD-1小鼠亚组的瘦素通过血脑屏障的转运严重受损。然而，目前尚不清楚这些小鼠是否天生具有BBB损伤或随着衰老和肥胖而获得。在这里，我们发现在其他正常的CD-1小鼠群体中，10%最胖的小鼠在12个月的寿命内体重增加，而10%最瘦的小鼠在3个月后体重几乎没有增加。最胖的小鼠在通过血脑屏障运输瘦素的能力上出现了进行性损伤，而最瘦的小鼠的运输速率不随年龄变化。肥胖小鼠禁食24小时或用瘦素治疗它们导致适度的体重减轻和瘦素跨血脑屏障的运输速率的发展与瘦小鼠相似。这些结果表明，在肥胖的CD-1小鼠中，瘦素穿过BBB的运输受损与肥胖症一起发展，并且即使适度的体重减轻也是可逆的。
Leptin resistance is a major cause of obesity in humans. A major component of this resistance is likely an impaired transport of leptin across the blood-brain barrier (BBB). The fattest subgroup of otherwise normal 12-mo-old CD-1 mice have severely impaired transport of leptin across the BBB. However, it is unknown whether these mice are born with a BBB impairment or acquire it with aging and obesity. Here, we found within an otherwise normal population of CD-1 mice that the 10% fattest mice gained weight throughout a 12-mo-life span, whereas the 10% thinnest mice gained little weight after 3 mo of age. The fattest mice acquired a progressive impairment in their ability to transport leptin across the BBB, whereas the thinnest mice had a rate of transport that did not change with age. Fasting fat mice for 24 h or treating them with leptin resulted in modest weight reduction and development of transport rates for leptin across the BBB similar to those of thin mice. These results show that, in obese CD-1 mice, the impaired transport of leptin across the BBB develops in tandem with obesity and is reversible with even modest weight reduction.