Association between circulating leptin and soluble receptors for tumor necrosis factor-alpha in hemodialysis patients

Abstract

Background: The expression of leptin, an adipocyte-derived protein, is regulated by tumor necrosis factor-alpha (TNF-alpha). Since circulating leptin levels adjusted for body fat mass are reported to be increased in dialysis patients, we examined if the TNF-alpha system may influence blood leptin levels in hemodialysis (HD) patients.

Patients and methods: Sixty-three stable HD patients who had no signs of infection, collagen disease or malignancy were enrolled in the study (age: 63 +/- 1 years, duration of HD: 14 +/- 1 years, male/female = 34/29). We measured serum leptin, TNF-alpha, soluble receptors for TNF-alpha (sTNFR p55, p80) and interleukin-6 (IL-6) concentrations with ELISA kits. Body fat mass was determined using DEXA. To evaluate the potential association between serum leptin and the TNF-alpha system, we compared serum leptin and sTNFR levels, which has been validated as a sensitive marker of activation of the TNF-alpha system.

Results: Serum leptin levels were significantly higher in female patients compared to male patients (14.07 +/- 3.60 vs. 4.26 +/- 0.85 ng/ml, p < 0.005). A strong correlation was found between serum leptin levels and estimated body fat mass both in males (r = 0.742, p < 0.0001) and females (r = 0.769, p < 0.001), respectively. Serum TNF-alpha, sTNFR p55, p80 and IL-6 levels were significantly increased in HD patients compared to normal subjects. However, no association was found between serum leptin and serum TNF-alpha, sTNFR p55, p80 and IL-6 levels. Serum leptin levels were significantly correlated with the atherosclerotic index both in men (r = 0.382, p = 0.027) and women (r = 0.281, p = 0.041). In contrast, there was no relationship between circulating leptin values and serum albumin, transferrin, creatinine levels, or normalized protein catabolic rate in each sex.

Conclusion: These findings suggested that serum leptin is independent of the TNF-alpha system, and is mainly correlated with body fat volume in HD patients. Elevation of circulating leptin may be associated with the disturbance of the serum lipid profile rather than malnutrition in patients receiving long-term HD.