Caro J F, Kolaczynski J W, Nyce M R, Ohannesian J P, Opentanova I, Goldman W H, Lynn R B, Zhang P L, Sinha M K, Considine R V
Division of Endocrinology, Diabetes and Metabolism, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Lancet. 1996 Jul 20;348(9021):159-61. doi: 10.1016/s0140-6736(96)03173-x.
A receptor for leptin has been cloned from the choroid plexus, the site of cerebrospinal-fluid (CSF) production and the location of the blood/cerebrospinal-fluid barrier. Thus, this receptor might serve as a transporter for leptin. We have studied leptin concentrations in serum and (CSF).
We demonstrated by radioimmunoassay and western blot the presence of leptin in human CSF. We then measured leptin in CSF and serum in 31 individuals with a wide range of bodyweight. Mean serum leptin was 318% higher in 8 obese (40.2 [SE 8.6] ng/mL) than in 23 lean individuals (9.6 [1.5] ng/mL, p < 0.0005). However, the CSF leptin concentration in obese individuals (0.337 [0.04] ng/mL) was only 30% higher than in lean people (0.259 [0.26] ng/mL, p < 0.1). Consequently, the leptin CSF/serum ratio in lean individuals (0.047 [0.010]) was 4.3-fold higher than that in obese individuals (0.011 [0.002], p < 0.05). The relation between CSF leptin and serum leptin was best described by a logarithmic function (r = 0 x 52, p < 0.01).
Our data suggest that leptin enters the brain by a saturable transport system. The capacity of leptin transport is lower in obese individuals, and may provide a mechanism for leptin resistance.
已从脉络丛中克隆出瘦素受体,脉络丛是脑脊液(CSF)的产生部位以及血脑屏障的所在位置。因此,该受体可能作为瘦素的转运体。我们研究了血清和脑脊液中的瘦素浓度。
我们通过放射免疫测定法和蛋白质印迹法证实了人脑脊液中存在瘦素。然后我们测量了31个体重范围广泛的个体的脑脊液和血清中的瘦素。8名肥胖者(40.2[标准误8.6]纳克/毫升)的平均血清瘦素比23名瘦人(9.6[1.5]纳克/毫升,p<0.0005)高318%。然而,肥胖个体的脑脊液瘦素浓度(0.337[0.04]纳克/毫升)仅比瘦人(0.259[0.2]纳克/毫升,p<0.1)高30%。因此,瘦人脑脊液/血清瘦素比值(0.047[0.010])比肥胖个体(0.011[0.002],p<0.05)高4.3倍。脑脊液瘦素与血清瘦素之间的关系用对数函数描述最佳(r = 0.52,p<0.01)。
我们的数据表明,瘦素通过一个可饱和转运系统进入大脑。肥胖个体中瘦素的转运能力较低,这可能为瘦素抵抗提供一种机制。