Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity

Fat tissue is a significant source of endogenous tumor necrosis factor alph a (TNF alpha), the pluripotent cytokine that plays an important role as a m ediator of the peripheral insulin resistance found in obesity. The majority of evidence for this role of TNF alpha is from studies in animal models of obesity. To explore further the role of TNF alpha in the pathogenesis of o besity-related insulin resistance in humans, we compared plasma levels of T NF alpha and the other main endocrine cytokine, interleukin-6 ([IL-6] both measured by enzyme-linked immunosorbent assay), in 26 obese women (body mas s index [BMI] > 30 kg/m(2)) and 13 female controls (BMI < 26 kg/m(2)) witho ut a history of recent or active infection. Glucose and insulin levels were measured at 0, 1, and 2 hours after a 75-g oral glucose load. There was no significant difference in plasma TNF alpha or IL-6 levels between obese an d non-obese subjects overall (2.10 +/- 0.19 v 1.65 +/- 0.18 pg/mL and 2.06 +/- 0.29 v 1.50 +/- 0.17 pg/mL, respectively). However, TNF alpha levels we re significantly elevated in obese subjects with a P-hour glucose level mor e than 140 mg/dL (n = 8) compared with the other obese subjects (n = 18) an d the non-obese controls (2.88 +/- 0.46 v 1.75 +/- 0.10 and 1.65 +/- 0.18 p g/mL, respectively, P < .01). Furthermore, the TNF alpha level correlated s ignificantly with the waist to hip ratio ([WHR] r = .53, P < .01) and fasti ng and post-oral glucose tolerance test (OGTT) insulin levels (r = .47, P < .02), but not with the BMI, and was higher in obese women with a WHR more than 0.90 (n = 14) in comparison to those with a WHR less than 0.90 (n = 12 , 2.47 +/- 0.29 v 1.66 +/- 0.18 pg/mL, respectively, P < .03). The correspo nding plasma leptin level was significantly higher in obese women versus th e control group (41.6 +/- 2.5 v 22.3 +/- 2.9 ng/mL, P < .001) and was relat ed to the BMI (r = .60, P < .01) but not to TNF alpha or the WHR. There wer e no significant differences in the corresponding IL-6 concentration betwee n groups, and IL-6 did not correlate with TNF(v, leptin, BMI, WHR, or insul in levels. In conclusion, circulating TNF alpha levels are higher in abdomi nal obesity compared with peripheral obesity, and may contribute to the ins ulin resistance that more commonly complicates the former pattern of fat di stribution. Copyright (C) 1999 by W.B. Saunders Company.