Smoking, fat mass and activation of the tumor necrosis factor-alpha pathway.

Abstract

Obesity may be associated with increased markers of inflammation that could be triggered by metabolic, physical, infectious or environmental processes. As smoking significantly increases cytokine production, we aimed to study how smoking influences the relationship between fat mass and soluble tumor necrosis factor-alpha (TNF-alpha) receptors 1 and 2 (sTNFR1 and sTNFR2). Cross-sectional, clinical observational study. A total of 133 healthy men (age: 27-53 y, body mass index (BMI): 24-30.2 kg/m(2)), 80 of whom were never-smokers and 53 smokers, matched for age, BMI and waist-to-hip ratio. Circulating soluble fractions of the TNF-alpha receptors sTNFR1 and sTNFR2 were measured to study their relationship with fat mass (bioelectric impedance). Smokers had significantly lower fat mass, lower fasting glucose, insulin and leptin concentrations than nonsmokers. Despite lower fat mass and insulin, smokers showed significantly increased circulating sTNFR2 levels (3.7+/-0.8 vs 3.4+/-0.7 ng/ml, P=0.03). The slopes of the relationships between sTNFR1 and fat mass, and between sTNFR2 and fat mass, were significantly steeper in smokers than in nonsmokers. In a stepwise multiple linear regression analysis, both fat mass (P<0.00001) and smoking (P=0.025) independently contributed to 13% of sTNFR1 variance and to 4% of sTNFR2 variance (P=0.03). Both fat mass and smoking are related to increased activity of the TNF-alpha axis.