Relationship between plasma leptin levels and the tumor necrosis factor-α system in obese subjects

OBJECTIVE: To evaluate the relationship between plasma leptin and the tumor necrosis factor-α (TNFα), TNF receptor p60 (TNF-R1) and TNF receptor p80 (TNF-R2) concentrations in obese subjects. DESIGN: Case-control study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital. MEASUREMENTS: Body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio (WHR), fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA IR), plasma leptin, TNFα, TNF-R1 and TNF-R2 concentrations were evaluated in obese subjects (n = 42) and in age- and gender-matched, lean healthy controls (n = 16). RESULTS: In obese subjects, fasting plasma glucose and insulin, HOMA IR, plasma leptin, TNFα, TNF-R1 and TNF-R2 concentrations were significantly higher than in controls. Furthermore, females showed higher leptin, TNF-R1 and TNF-R2 plasma concentrations compared to males, in both control and obese subjects. In control subjects, plasma leptin concentrations showed a direct correlation with BMI (r = 0.74, P <0.001), hip circumference (r = 0.94, P <0.001), TNF-R1 (r = 0.79, P <0.001) and TNF-R2 (r = 0.64, P <0.01), and a negative correlation with WHR (r = -0.58, P <0.05). In obese subjects, we found a direct correlation between plasma leptin concentrations and BMI (r = 0.67, P <0.001), hip circumference (r = 0.66, P <0.001), fasting glucose (r = 0.37, P <0.05), fasting insulin (r = 0.31, P <0.05), HOMA IR (r = 0.38, P <0.05), TNF-R1 (r = 0.71, P <0.001) and TNR-R2 (r = 0.66, P <0.001), while a negative correlation was found between circulating leptin and WHR (r = -0.44, P <0.01). In multivariate analysis, plasma leptin concentrations were significantly associated with BMI (P = 0.015) and gender (P = 0.047) in the control group, while in obese subjects, plasma leptin showed a significant association with BMI (P = 0.019) and TNF-R1 (P = 0.012). CONCLUSIONS: Our results are consistent with the hypothesis that the TNFα system could be involved in the regulation of plasma leptin concentrations in obese subjects.