BACKGROUND: C-reactive protein (CRP) concentrations have been found to be higher in premenopausal women than in men, whereas interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) concentrations have been reported to be lower in women than in men. OBJECTIVE: The objective was to determine whether the sex difference in body fat distribution accounts for the observed sex differences in inflammatory markers. DESIGN: Plasma CRP, IL-6, and TNF-alpha concentrations were measured in 208 healthy men (age: 42.2 +/- 15.2 y) and in 145 healthy women (age: 36.8 +/- 11.1 y). RESULTS: Compared with men, premenopausal women had higher CRP concentrations 1.24 (25th percentile: 0.54; 75th percentile: 3.04) compared with 0.94 (0.51, 2.40) mg/L; P < 0.05 and lower plasma TNF-alpha concentrations 1.50 (25th percentile: 1.23; 75th percentile: 1.82) compared with 1.71 (1.40, 2.05) pg/mL; P < 0.001. No sex difference in IL-6 concentrations was noted. Regression analyses indicated that the relation between CRP or IL-6 and visceral adipose tissue (VAT) and subcutaneous AT (SAT) was sex-specific; a significantly steeper slope was observed in women than in men (P < 0.05). Sex differences in CRP concentrations were abolished after SAT was adjusted for. In a multivariate model of the whole sample, we found that both SAT and VAT and the sex x SAT interaction term were significant correlates of CRP and IL-6 concentrations. Finally, whereas CRP concentrations were largely influenced by visceral adiposity in men, subcutaneous adiposity was the key correlate of CRP in women. CONCLUSION: The higher CRP concentrations found in women appear to be due to their greater accumulation of subcutaneous fat than that observed in men.
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