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.


METHODS
Cross-sectional study.


METHODS
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.


CONCLUSIONS
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.
Chu
N F
NF
Department of Epidemiology, Harvard School Public Health, Boston, MA, USA. chuepi@ndmctsgh.edu.tw
Spiegelman
D
D
Rifai
N
N
Hotamisligil
G S
GS
Rimm
E B
EB
D015703:Antigens, CD / Q000097:blood; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II
D015703:Antigens, CD; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin; D020738:Leptin; D054411:Receptors, Leptin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C515448:LEPR protein, human