Plasma levels of soluble tumor necrosis factor-alpha receptors are related to total and LDL-cholesterol in lean, but not in obese subjects.

Background: Tumor necrosis factor-alpha (TNFalpha) is a mediator of insulin resistance. Plasma levels of soluble TNFalpha receptors (sTNFR1 and sTNFR2) probably reflect paracrine action of the cytokine. TNFalpha is also a regulator of lipid metabolism, however, data about impact of obesity on the relationships between TNFalpha and plasma lipids remain controversial.

Aim: The purpose of the present study was to examine the associations of TNFalpha system with plasma lipids in lean and obese subjects with normal glucose metabolism.

Methods: We examined 63 subjects, 33 lean (BMI<25 kg x m(-2)) and 30 with marked overweight or obesity (BMI>27.8 kg x m(-2)). Anthropometric and biochemical parameters were measured. Oral glucose tolerance test and euglycemic hyperinsulinemic clamp were also performed.

Results: Obese subjects were markedly more insulin resistant and had higher levels of both TNFalpha receptors. Total (TC) and LDL-cholesterol (LDL-C), triglycerides (TG) and non-esterified fatty acids (NEFA) were also higher in the obese group. In obese subjects, both receptors were significantly related to TG and HDL-cholesterol (HDL-C), while sTNFR2 was also associated with NEFA. All those correlations disappeared after controlling for insulin sensitivity. In lean subjects, both receptors were related to TC, HDL-C and LDL-C. In that group, sTNFR1 predicted values of all those parameters independently of BMI, plasma glucose and insulin, and insulin sensitivity.

Conclusion: We conclude that TNFalpha receptors are associated with plasma lipids in different way in lean and in obese subjects. TNFalpha system is probably important in determining cholesterol levels in lean subjects, while in obese this effect might be masked by other metabolic abnormalities.