Effect of One Morning Meal and a Bolus of Dexamethasone on 24‐Hour Variation of Serum Leptin Levels in Humans

Objective: We have previously shown that morning administration of dexamethasone in combination with food induces a doubling of serum leptin levels starting at 7 hours after dexamethasone administration, with a maximum effect at 10 hours, the latest time point that we have studied. However, dexamethasone given in the absence of food had no effect on serum leptin at 10 hours. The present experiment was undertaken to determine the duration of the effect of dexamethasone on 24‐hour serum leptin under fasted and fed conditions in humans. Research Methods and Procedures: Six healthy non‐obese male volunteers were studied under the following four conditions: 1) dexamethasone (2 mg intravenously, given at 0900 hours) with fasting; 2) dexamethasone with food (1700 kcal, 55% carbohydrate, 15% protein, and 30% fat, given in one meal 2 hours after dexamethasone administration at 1100 hours); 3) saline with food (same meal); 4) saline with fasting. Serum leptin, glucose, insulin, and cortisol were monitored every 30 minutes for 24 hours. Results: 1) Under the fasting condition, dexamethasone increased leptin nocturnal secretion between 2100 and 2400 hours. 2) A single meal (1700 kcal) at 1100 hours increased nocturnal leptin secretion when compared with the fasting condition. The peak increase of leptin was 123% over baseline between 2100 and 2400 hours, 10 to 14 hours after the meal. 3) In the fed + dexamethasone condition, leptin levels increased from baseline starting 8 hours after dexamethasone injection, reached a maximum increase of 260% between 2100 and 2400 hours, then decreased thereafter, remaining elevated compared to baseline for 16 hours. There was a correlation between 24‐hour leptin secretion and insulin secretion after a single morning meal. Discussion: A single bolus of dexamethasone, given before a single large meal, produces a delayed (6‐hour) but long‐lasting increase in serum leptin (over 16 hours). Under fasted conditions, dexamethasone does not increase daytime leptin but does increase leptin during the night.