Leptin production in adipocytes from morbidly obese subjects: Stimulation by dexamethasone, inhibition with troglitazone, and influence of gender

This study examined the regulation of leptin production by dexamethasone an d troglitazone. Subcutaneous and omental adipose tissue was obtained during bariatric surgical procedures (30 women and 16 men; body mass index, 52.5 +/- 1.7 kg/m(2), age, 39 +/- 2 yr), and adipocytes were cultured in suspens ion. Subcutaneous adipocytes from females released significantly more lepti n than did omental cells from the same subject (P < 0.05), but basal leptin release was not different in adipocytes from these depots in males. Dexame thasone (0.1 <mu>mol/L) significantly increased leptin release within 24 h from sc (135 +/- 13% of control) and omental (227 +/- 53%) adipocytes of fe males, but not males. Dexamethasone-stimulated leptin production at 48 h wa s significantly greater in the omental adipocytes of females (398 +/- 64% o f control) than in sc adipocytes of females (207 +/- 21%) or the omental (2 11 +/- 33%) and sc (180 +/- 23%) adipocytes of males. Troglitazone (10 mu m ol/L; 48 h) significantly inhibited dexamethasone-stimulated leptin release in sc (57 +/- 10.7% inhibition) and omental adipocytes (134 +/- 26% inhibi tion). There was no gender-related difference in the effect of troglitazone to inhibit dexamethasone-stimulated leptin release. Troglitazone significa ntly inhibited basal leptin production from omental adipocytes by 15.0 +/- 5.2%. The effect of dexamethasone and troglitazone to regulate leptin relea se was mediated through changes in ob gene expression, but did not involve changes in glucose uptake or metabolism to lactate. The data suggest that adipocytes from females are more responsive to the st imulatory effect of dexamethasone in vitro than are adipocytes from males. If adipocytes from females are more responsive to relevant in vivo stimuli for leptin secretion such as insulin or glucose, this could contribute to t he gender difference in serum leptin. The data also suggest that leptin rel ease from omental adipocytes may be more responsive to hormonal and nutrien t regulation in vivo than are sc adipocytes.