TUMOR-NECROSIS-FACTOR-ALPHA 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 al pha) expression, that this expression falls with weight loss, and that TNF alpha may specifically inhibit insulin action, the possibility th at TNF alpha may be a mediator of insulin resistance has been raised. We have undertaken this study to investigate whether serum TNF alpha c oncentrations are elevated in obese subjects, whether they fall after weight loss, and whether this fall parallels the fall in insulin relea se after glucose challenge. Obese patients (age range: 25-54, weight m ean +/- SD: 96.4 +/- 13.8 kg, body mass index: 35.7 +/- 5.6 kg/m(2)) w ere 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 T NF 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 fe ll significantly (2.63 +/- 1.40 pg/mL) after weight loss (P < 0.02). T he magnitude of insulin release after glucose (75 g) challenge (area u nder the curve) also fell significantly (P < 0.01) after weight loss. The magnitude of weight loss and fall in TNF alpha were related to bas al 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 t hat obesity is associated with increased plasma TNF alpha concentratio ns, which fall with weight loss. Because circulating TNF alpha may med iate insulin resistance in the obese, a fall in TNF alpha concentratio ns may contribute to the restoration of insulin resistance after weigh t loss, Thus, TNF alpha may be an important circulating cytokine, whic h may provide a potentially reversible mechanism for mediating insulin resistance.