Tumor necrosis factor-α in sera of obese patients:: Fall with weight loss

In view of the recent demonstration that obesity in animals and humans is associated with an increase in tumor necrosis factor-alpha (TNF alpha) expression, that this expression falls with weight loss, and that TNF alpha may specifically inhibit insulin action, the possibility that TNF alpha may be a mediator of insulin resistance has been raised. We have undertaken this study to investigate whether serum TNF alpha concentrations are elevated in obese subjects, whether they fall after weight loss, and whether this fall parallels the fall in insulin release after glucose challenge. Obese patients (age range: 25-54, weight mean +/- SD: 96.4 +/- 13.8 kg, body mass index: 35.7 +/- 5.6 kg/m(2)) were started on a diet program. The mean weight fell to 84.5 +/- 11.3 (P < 0.0001) and body mass index to 31.3 +/- 4.9 (P < 0.0001). Plasma TNF alpha concentrations were markedly elevated in the obese (3.45 +/- 0.16 pg/mL), when compared with controls (0.72 +/- 0.28 pg/mL), and fell significantly (2.63 +/- 1.40 pg/mL) after weight loss (P < 0.02). The magnitude of insulin release after glucose (75 g) challenge (area under the curve) also fell significantly (P < 0.01) after weight loss. The magnitude of weight loss and fall in TNF alpha were related to basal body weight (r = 0.57, P < 0.001) and basal TNF alpha (r = 0.55, P < 0.001) concentrations, respectively, but not to each other or to the glucose-induced insulin release (area under the curve). We conclude that obesity is associated with increased plasma TNF alpha concentrations, which fall with weight loss. Because circulating TNF alpha may mediate insulin resistance in the obese, a fall in TNF alpha concentrations may contribute to the restoration of insulin resistance after weight loss, Thus, TNF alpha may be an important circulating cytokine, which may provide a potentially reversible mechanism for mediating insulin resistance.