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

OBJECTIVE: To evaluate the relationship between plasma leptin and the tumor necrosis factor-alpha (TNF alpha), TNF receptor pen (TNF-R1) and TNF recep tor p80 (TNF-R2) concentrations in obese subjects. DESIGN: Case-control study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at th e 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 lepti n, TNF alpha, TNF-R1 and TNF-RS concentrations were evaluated in obese subj ects (n = 42) and in age- and gender-matched, lean healthy controls (n = 16 ). RESULTS: In obese subjects, fasting plasma glucose and insulin, HOMA IR, pl asma leptin, TNF alpha, 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 ob ese subjects. In control subjects, plasma leptin concentrations showed a di rect 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 dire ct correlation between plasma leptin concentrations and BMI (r=0.67, P<0.00 1), 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 fo und between circulating leptin and WHR (r=-0.44, P<0.01), In multivariate a nalysis, plasma leptin concentrations were significantly associated with BM I (P=0.015) and gender (P=0.047) in the control group, while in obese subje cts, 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 TNF al pha system could be involved in the regulation of plasma leptin concentrati ons in obese subjects.