Tumor necrosis factor-alpha 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-alpha (TNFalpha). Adipocytes were isolated from adipose tissue obtained during bariatric surgical procedures (17 women and 3 men; body mass index, 52.5 +/- 2.4 kg/m2; age, 40 +/- 3 yr) and cultured in suspension. Leptin release from sc adipocytes was inhibited 17.7 +/- 5.2% (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 TNFalpha, 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. TNFalpha (10 ng/mL) had no effect on dexamethasone (0.1 micromol/L)-stimulated leptin production in sc adipocytes. In omental adipocytes TNFalpha 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 ofleptin release from omental adipocytes was observed at 24 h with 100 ng/mL TNFalpha (P < 0.05). Anti-TNFalpha antibody completely blocked TNFalpha inhibition of leptin release. The ob messenger ribonucleic acid was significantly reduced (23.6 +/- 5.9%) after 48 h of TNFalpha (100 ng/mL) treatment (P < 0.025). TNFalpha 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 TNFalpha is inhibition of leptin production.
Fawcett
R L
RL
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
Waechter
A S
AS
Williams
L B
LB
Zhang
P
P
Louie
R
R
Jones
R
R
Inman
M
M
Huse
J
J
Considine
R V
RV
D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004338:Drug Combinations; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008297:Male; D009767:Obesity, Morbid / Q000378:metabolism* / Q000473:pathology*; D009852:Omentum; D012867:Skin; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004338:Drug Combinations; D005938:Glucocorticoids; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone