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Inhibiting Endogenous Cortisol Blunts the Meal-Entrained Rise in Serum Leptin

Obesity Research Center, St. Luke’s/Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York 10025

Address all correspondence and requests for reprints to: Dr. Blandine Laferrère, Obesity Research Center, St. Luke’s/Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, 1111 Amsterdam Avenue, New York, New York 10025.

Context: Administration of glucocorticoids increases serum leptin levels in lean and obese individuals. A morning meal produces an increase in insulin, a cortisol peak, and an increase in leptin; these changes do not occur during fasting.

Objective: The objective of this study was to investigate whether inhibiting endogenous cortisol secretion with metyrapone decreases 24-h serum leptin levels and to determine whether a meal-related midmorning surge in cortisol is a prerequisite for the meal-entrained nocturnal rise in leptin.

Design: This was a randomized, cross-over study.

Setting: The study was performed at the General Clinical Research Center.

Participants: Lean males were studied.

Intervention: In study 1, seven lean men were studied for 24 h while their endogenous cortisol secretions were manipulated as follows: 1) CONTROL; 2) cortisol suppression by metyrapone (MET); and 3) MET and oral hydrocortisone (at 0900 h) (MET + CORT). Subjects were all fed a eucaloric diet (two meals at 1100 and 1700 h). In study 2, six men were studied without pharmacological intervention for 24 h on two occasions: once under a complete fast (FAST) and once in a feeding condition (one meal at 1100 h; FED).

Main Outcome Measure: The main outcome measure was serum leptin.

Results: MET significantly suppressed serum cortisol at 0800 h, midmorning, and over the 24-h period. As a result of cortisol suppression, 24-h serum leptin levels were decreased vs. control values despite similar insulin responses to meals. Administering a single dose of hydrocortisone to MET subjects potently stimulated serum leptin compared with the effect of MET alone.

Conclusions: Our data demonstrate that endogenous cortisol secretion is necessary for the maintenance of serum leptin levels over 24 h in lean, normally fed males.

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