Glycemic status and soluble tumor necrosis factor receptor levels in relation to plasma leptin concentrations among normal weight and overweight US men

OBJECTIVE: 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 lev els, 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-de rived cytokines in regulating plasma leptin levels among normal and overwei ght men. DESIGN: Cross-sectional study. SUBJECTS AND MEASUREMENTS: We measured plasma leptin, insulin, c-peptide an d plasma soluble tumor necrosis factor receptor (sTNF-R) concentrations in 178 men. The subjects were selected from the Health Professionals Followup 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. RESULTS: Men in the highest quintile of plasma leptin (mean = 12.7 ng/ml) w eighed more, were less physically active and had higher circulating insulin , c-peptide, sTNF-R1 and sTNF-R2 concentrations than men in the lowest quin tile (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 posi tively associated with plasma leptin after further adjusting for body mass index and other metabolic parameters of interest. Interestingly, these obse rved associations were limited to men with a BMI greater than or equal to 2 5 kg/m(2). CONCLUSION: Our results suggest that glucose homeostasis and the activity o f the TNF system may modulate leptin secretion and production among overwei ght men. Glucose homeostasis and TNF-alpha is important in metabolic disord ers related to hyperleptinemia.