Variations in glucocorticoid levels within the physiological range affect plasma leptin levels.

OBJECTIVE Leptin, the obese gene product, is thought to regulate body fat through its action on hypothalamic receptors that influence satiety. The hormonal regulation of leptin is important, since it might affect adiposity. Leptin regulation in man is poorly understood. We studied the relation between endogenous cortisol and leptin levels as well as the acute and chronic effects of a low dose of dexamethasone (DEX) on plasma leptin levels in healthy male volunteers. SUBJECTS AND EXPERIMENTAL PROTOCOL: The correlation between basal plasma levels of leptin and cortisol and the chronic effect of DEX treatment were studied in 12 subjects. Plasma leptin and cortisol levels were determined every other hour for 24 h, before and after 2 weeks of oral administration of 0.1 mg DEX twice daily. The acute effect was studied in 20 subjects, who received 1 mg DEX at 2300 h. Fasting blood samples were taken at 0800 h on the same day (i.e. before DEX) and on the day after. RESULTS Under basal conditions, we found a correlation between mean plasma levels of leptin and cortisol (r = 0.7, P<0.02). Mean plasma leptin levels had increased by 50% after 2 weeks of DEX treatment (P<0.05). The circadian rhythm of leptin was preserved, but the night peak occurred 2.5 h earlier (P<0.05). Fasting plasma leptin levels were 20% higher 9 h after 1 mg DEX orally than at the same time on the day before (P<0.002). CONCLUSION Physiological variations in cortisol are involved in the regulation of leptin.