Impaired transport of leptin across the blood-brain barrier in obesity
Impaired transport of leptin across the blood-brain barrier in obesity
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DOI：
10.1016/s0196-9781(99)00139-4
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发表时间：
1999-11-01
期刊：
影响因子：
3
通讯作者：
Farrell, CL
中科院分区：
文献类型：
--
作者：
Banks, WA;DiPalma, CR;Farrell, CL
瘦素是由脂肪细胞分泌的17-kDa蛋白，其通过穿过血脑屏障（BBB）影响进食和产热来调节身体肥胖。饮食性肥胖的肥胖人类和啮齿动物模型显示对血液传播的瘦素的敏感性降低，推测是由于瘦素穿过BBB的运输受损。我们在这里表明，在12个月大的肥胖CD-1小鼠中，瘦素通过血脑屏障的转运率降低了约2/3。在后续研究中，使用了一种灌注方法，用含有低浓度放射性瘦素的缓冲液代替血液。肥胖小鼠的转运率仍然低于瘦小鼠，这表明与肥胖相关的转运率降低并不像人们认为的那样仅仅是由于继发于较高血清瘦素水平的转运蛋白饱和，而是由于血脑屏障转运瘦素的能力降低。这表明了一种新的肥胖模型，其中瘦素进入CNS的BBB运输缺陷是对瘦素不敏感的基础，并导致肥胖。(C)1999 Elsevier Science Inc. All rights reserved.
Leptin is a 17-kDa protein secreted by fat cells that regulates body adiposity by crossing the blood-brain barrier (BBB) to affect feeding and thermogenesis. Obese human and rodent models of dietary obesity have shown decreased sensitivity to blood-borne leptin, postulated to be due to impaired transport of leptin across the BBB. We show here that the transport rate of leptin across the BBB is reduced about 2/3 in 12-month-old obese CD-I mice. In a follow-up study, a perfusion method was used that replaced the blood with a buffer containing low concentrations of radioactive leptin. Obese mice still had lower rates of transport into the brain than lean mice, which shows that the reduction in transport rate associated with obesity is not due simply to saturation of transporter secondary to higher serum leptin levels as has been thought, but to a decreased capacity of the BBB to transport leptin. This suggests a new model for obesity in which a defect in the BBB transport of leptin into the CNS underlies the insensitivity to leptin and leads to obesity. (C) 1999 Elsevier Science Inc. All rights reserved.