Plasma soluble tumor necrosis factor alpha receptors and leptin levels in normal-weight and obese women: effect of adiposity and diabetes.

Abstract

To explore the determinants of the tumor necrosis factor alpha (TNFalpha) system and their relationship with plasma leptin levels. We studied a cohort of 157 diabetic and non-diabetic females with a wide range of adiposity distributed into five groups: control--body mass index (BMI) between 19 and 27 kg/m(2) (n=24); obese--BMI between 27 and 40 kg/m(2) (n=63); obese type 2 diabetes mellitus--BMI between 27 and 40 kg/m(2) with diabetes mellitus (n=19); morbid obese--BMI >40 kg/m(2) (n=29); and morbid obese type 2 diabetes mellitus--BMI >40 kg/m(2) with diabetes (n=22). Fasting glucose levels, plasma total triglycerides and cholesterol, high-, low- and very low-density lipoprotein cholesterol were assayed by enzymatic and colorimetric methods. Plasma TNFalpha levels were measured by ELISA assay and insulin and leptin levels by radioimmunoenzymatic assays. Both soluble TNFalpha (sTNFalpha) receptors were measured by immunoenzymometric assays. All groups of patients showed significant increases in both sTNFalpha receptors relative to control. sTNFalpha receptor 1 (sTNFR1) was higher in morbid obese diabetic individuals compared with their non-diabetic counterparts (P=0.003), while sTNFR2 was significantly different between obese and morbid obese subjects (P=0.036). Bivariate correlation analysis showed a significant relationship between both plasma sTNFalpha receptors and BMI, percentage of body fat, fasting glucose, insulin and leptin. In multivariate analysis, both sTNF receptor plasma levels were predicted by percentage of body fat and the presence of diabetes (R(2)=0.20 for sTNFR1 and sTNFR2). When plasma leptin levels were added into the model, this protein and the presence of diabetes explained 27% of the variance of the plasma sTNFR1 levels. The presence of diabetes, adiposity or leptin levels are independent determinants of both sTNFalpha receptors. The independent association between plasma TNFalpha receptors and leptin levels in obese patients is consistent with the hypothesis that these proteins could be involved in the same pathway that regulates body adiposity.