Tumor necrosis factor-α inhibits leptin production in subcutaneous and omental adipocytes from morbidly obese humans

This study was undertaken to examine the regulation of leptin production from human adipocytes by tumor necrosis factor-a (TNF alpha). Adipocytes were isolated hom adipose tissue obtained during bariatric surgical procedures (17 women and 3 men; body mass index, 52.5 +/- 2.4 kg/m(2); age, 40 +/- 3 yr) and cultured in suspension. Leptin release from sc adipocytes was inhibited 17.7 +/- 5.25 (P < 0.01), 21.6 +/- 4.3% (P < 0.005), and 37.1 +/- 7.2% (P < 0.05) by 1, 10, and 100 ng/mL TNF alpha, respectively, after 48 h in culture. At 100 ng/mL, significant inhibition of leptin release (25.8 +/- 9.7%; P < 0.05) was detected by 24 h. TNF alpha (10 ng/mL) had no effect on dexamethasone (0.1 mu mol/L)-stimulated leptin production in sc adipocytes. In omental adipocytes TNF alpha inhibited leptin release 21.0 +/- 9.6% and 40.8 +/- 6.3% at 10 and 100 ng/mL by 48 h (P < 0.05). Significant inhibition of leptin release from omental adipocytes was observed at 24 h with 100 ng/mL TNF alpha (P < 0.05). Anti-TNF alpha antibody completely blocked TNF alpha inhibition of leptin release. The ob messenger ribonucleic acid was significantly reduced (23.6 +/- 5.9%) after 48 h of TNF alpha (100 ng/mL) treatment (P < 0.025). TNF alpha had no effect on glucose uptake or lactate production in sc and omental adipocytes. The data suggest that the direct paracrine effect of adipose-derived TNF alpha is inhibition of leptin production.