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 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. DESIGN: Cross-sectional study. SUBJECTS AND MEASUREMENTS: 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 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) 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 greater than or equal to 25 kg/m(2). CONCLUSION: 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.