Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence

Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence
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DOI:
10.1210/jc.2002-020001
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发表时间:
2002-10-01
影响因子:
5.8
通讯作者:
Kiess, W
Kiess, W
中科院分区:
医学2区
文献类型:
--
作者:
Kratzsch, J;Lammert, A;Kiess, W

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瘦素在人血液中通过一种高亲和力结合蛋白结合,这种结合蛋白似乎与可溶性瘦素受体(sOB-R)相同。我们使用配体介导的免疫功能测定法测定血清sOB-R,研究了581名健康儿童和青少年以及13名神经性厌食症患者在儿童期、青春期和青春期的病程。在生命的最初几年,sOB-R的浓度非常高。此后,sOB-R水平持续下降。因此,相关分析表明,sOB-R与年龄、IGF-I水平、青春期、生理和身体成分参数以及瘦素浓度呈显著负相关(P < 0.001)。多元回归分析显示,身高、IGF-I和年龄(仅在女孩中)是sOB-R水平的独立预测因子;这些变量分别约占男孩和女孩sOB-R水平变化的65%和48%。游离瘦素指数(FLI,瘦素与sOB-R水平之比)和瘦素水平的年龄依赖中值的过程在两性中是平行的。相关分析表明,生长和性成熟的特定参数与FLI的关系比瘦素更密切;这种亲密关系在男孩中更为明显。神经性厌食症患者体重增加导致瘦素和IGF-I水平显著升高(P < 0.01),而sOB-R值中位数降低(P < 0.01)。sOB-R与IGF-I水平再次呈显著相关(r = -0.55, P < 0.01)。这些发现表明,在能量缺乏时,高水平的sOB-R可能反映了sOB-R的上调以抑制瘦素的作用。此外,测定sOB-R和FLI是研究生长和性成熟过程中瘦素轴的额外有价值的工具。
Leptin is bound in human blood by a high affinity binding protein, which appears to be identical with the soluble leptin receptor (sOB-R). Using a ligand-mediated immunofunctional assay for the determination of serum sOB-R, we investigated its course during childhood, puberty, and adolescence in a large cohort of 581 healthy children and adolescents and a small group of 13 patients with anorexia nervosa. In the first years of life, sOB-R is detectable in remarkably high concentrations. Thereafter, a continuous decline of sOB-R levels was found. Consequently, correlation analyses demonstrated significant inverse relationships (P < 0.001) of sOB-R with age, IGF-I levels, pubertal stage, auxological and body composition parameters, as well as with leptin concentrations. Multiple regression analysis revealed that height, IGF-I, and age (only in girls) were independent predictors of sOB-R levels; these variables account for approximately 65% and 48% of the variation of sOB-R levels in boys and girls, respectively. The courses of age-dependent median values for the free leptin index (FLI, ratio between leptin and sOB-R levels) and for leptin levels were parallel in both genders. Correlation analyses demonstrated that in particular parameters of growth and sexual maturation are more closely related to the FLI than to leptin alone; this closer relationship is more pronounced among boys. Weight gains of patients with anorexia nervosa resulted in a significant increase in leptin and IGF-I levels (P < 0.01), whereas the median of sOB-R values decreased (P < 0.01). sOB-R and IGF-I levels were again significantly correlated (r = -0.55, P < 0.01). These findings suggest that high levels of sOB-R in emaciation may reflect an upregulation of the sOB-R to suppress leptin action during energy deficiency. Furthermore, determinations of sOB-R and FLI are additional valuable tools to investigate the leptin axis during growth and sexual maturation.