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

Int J Obes Relat Metab Disord. 2000 Sep;24(9):1085-92. doi: 10.1038/sj.ijo.0801361.


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 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.

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 > or = 25 kg/m2.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / blood
  • Body Mass Index
  • C-Peptide / blood
  • Case-Control Studies
  • Cross-Sectional Studies
  • Glycated Hemoglobin / metabolism*
  • Humans
  • Insulin / blood
  • Leptin / blood*
  • Male
  • Middle Aged
  • Obesity / blood*
  • Receptors, Leptin
  • Receptors, Tumor Necrosis Factor / blood*
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II


  • Antigens, CD
  • C-Peptide
  • Glycated Hemoglobin A
  • Insulin
  • LEPR protein, human
  • Leptin
  • Receptors, Leptin
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II