Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin -: Observational and interventional studies in humans
Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin -: Observational and interventional studies in humans
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DOI：
10.2337/diabetes.51.7.2105
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发表时间：
2002-07-01
期刊：
影响因子：
7.7
通讯作者：
Mantzoros, CS
中科院分区：
文献类型：
--
作者：
Chan, JL;Blüher, S;Mantzoros, CS
瘦素是一种脂肪细胞分泌的激素，在能量平衡和多种生理过程中起重要作用。瘦素受体的循环可溶形式[可溶性瘦素受体（sOB-R）]是主要的瘦素结合蛋白和游离瘦素指数（FLI）的决定因素，游离瘦素指数（FLI）是瘦素的假定生物活性形式。我们进行了观察性和干预性研究，以阐明人体sOB-R和FLI的调节。在一项横断面研究（n = 118）中，瘦素、性别和肥胖是sOB-R的重要决定因素。多因素分析显示，雌二醇（E2）和睾酮对sOB-R有预测作用，而雌二醇（E2）和睾酮对sOB-R有预测作用。胰岛素预测瘦素和FLI。在一项频率采样研究（n = 6）中，sOB-R遵循与瘦素相反的显著昼夜节律，表明瘦素的生物活性可能具有比最初认为的更明显的昼夜变化。一个72小时的快速在8名男子瘦素水平下降了80%，增加淋巴细胞瘦素受体mRNA的表达和血清sOB-R水平的100%。给予禁食男性生理和药理剂量的重组甲硫氨酰人瘦素（rhLeptin）可防止禁食诱导的sOB-R水平升高，而药理剂量导致sOB-R水平降低。这些研究提供了sOB-R受性别、肥胖、激素和rhLeptin给药调节的证据。这可能对瘦素在与异常瘦素水平相关的疾病状态（例如，肥胖和神经性厌食症）。
Leptin is an adipocyte-secreted hormone important in energy homeostasis and diverse physiological processes. A circulating soluble form of the leptin receptor [soluble leptin receptor (sOB-R)] is the main leptin-binding protein and determinant of free leptin index (FLI), the presumed biologically active form of leptin. We performed observational and interventional studies to elucidate the regulation of sOB-R and FLI in humans. In a cross-sectional study (n = 118), leptin, gender, and adiposity were significant determinants of sOB-R. By multivariate analysis, estradiol (E2) and testosterone predict sOB-R, whereas. insulin predicts leptin and FLI. In a frequent-sampling study (n = 6), sOB-R followed a significant circadian rhythm inverse to that of leptin, suggesting that leptin's biological activity may have an even more pronounced diurnal variation than originally thought. A 72-h fast in eight men decreased leptin levels by 80% and increased lymphocyte expression of leptin receptor mRNA and serum sOB-R levels by 100%. Physiological and pharmacological doses of recombinant-methionyl human leptin (rhLeptin) administered to fasted men prevented the fasting-induced increase of sOB-R levels, and pharmacological doses resulted in a decrease in sOB-R levels. These studies provide evidence that sOB-R is regulated by gender, adiposity, hormones, and rhLeptin administration. This may have important implications' for the biological activity of leptin in disease states associated with abnormal leptin levels (e.g., obesity and anorexia nervosa).