Chu N F, Spiegelman D, Rifai N, Hotamisligil G S, Rimm E B
Department of Epidemiology, Harvard School Public Health, Boston, MA, USA.
Int J Obes Relat Metab Disord. 2000 Sep;24(9):1085-92. doi: 10.1038/sj.ijo.0801361.
Leptin, an adipocyte-derived protein product of the obesity (ob) gene, is a multifunctional polypeptide associated with the development of obesity-related disorders in humans. There is considerable inter-individual variation in plasma leptin even among subjects with comparable obesity levels, which suggests that factors other than adipose mass may be involved in the regulation of leptin expression and/or production. The purpose of this study was to evaluate the potential role of glycemic status and adipose-derived cytokines in regulating plasma leptin levels among normal and overweight men.
Cross-sectional study.
We measured plasma leptin, insulin, c-peptide and plasma soluble tumor necrosis factor receptor (sTNF-R) concentrations in 178 men. The subjects were selected from the Health Professionals Follow-up Study (HPFS), and aged 47-64 y in 1994, were free of cardiovascular disease, diabetes mellitus, malignant neoplasms, and had provided a fasting blood sample and a detailed lifestyle questionnaire.
Men in the highest quintile of plasma leptin (mean = 12.7 ng/ml) weighed more, were less physically active and had higher circulating insulin, c-peptide, sTNF-R1 and sTNF-R2 concentrations than men in the lowest quintile (mean = 2.8 ng/ml). We found a significant correlation between plasma insulin, c-peptide, glycosylated hemoglobin (HbA1c), and sTNF-R1 on leptin concentrations (with Spearman correlation coefficients ranging from 0.17 to 0.48 and all P < 0.05). Only HbA1c and sTNF-R1 were independently and positively associated with plasma leptin after further adjusting for body mass index and other metabolic parameters of interest. Interestingly, these observed associations were limited to men with a BMI > or = 25 kg/m2.
Our results suggest that glucose homeostasis and the activity of the TNF system may modulate leptin secretion and production among overweight men. Glucose homeostasis and TNF-alpha is important in metabolic disorders related to hyperleptinemia.
瘦素是肥胖（ob）基因的脂肪细胞衍生蛋白产物，是一种与人类肥胖相关疾病发展相关的多功能多肽。即使在肥胖水平相当的受试者中，血浆瘦素也存在相当大的个体间差异，这表明除脂肪量外的其他因素可能参与瘦素表达和/或产生的调节。本研究的目的是评估血糖状态和脂肪衍生细胞因子在调节正常和超重男性血浆瘦素水平中的潜在作用。
横断面研究。
我们测量了178名男性的血浆瘦素、胰岛素、C肽和血浆可溶性肿瘤坏死因子受体（sTNF-R）浓度。受试者选自健康专业人员随访研究（HPFS），1994年年龄在47 - 64岁，无心血管疾病、糖尿病、恶性肿瘤，并提供了空腹血样和详细的生活方式问卷。
血浆瘦素最高五分位数组（平均 = 12.7 ng/ml）的男性比最低五分位数组（平均 = 2.8 ng/ml）的男性体重更重、身体活动更少，且循环胰岛素、C肽、sTNF-R1和sTNF-R2浓度更高。我们发现血浆胰岛素、C肽、糖化血红蛋白（HbA1c）和sTNF-R1与瘦素浓度之间存在显著相关性（Spearman相关系数范围为0.17至0.48，所有P < 0.05）。在进一步调整体重指数和其他感兴趣的代谢参数后，只有HbA1c和sTNF-R1与血浆瘦素独立且呈正相关。有趣的是，这些观察到的关联仅限于BMI≥25 kg/m2的男性。
我们的结果表明，葡萄糖稳态和TNF系统的活性可能调节超重男性的瘦素分泌和产生。葡萄糖稳态和TNF-α在与高瘦素血症相关的代谢紊乱中很重要。
