Inhibiting endogenous cortisol blunts the meal-entrained rise in serum leptin.
BACKGROUND
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.


METHODS
This was a randomized, cross-over study.


METHODS
The study was performed at the General Clinical Research Center.


METHODS
Lean males were studied.


METHODS
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).


METHODS
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.
Obesity Research Center, St. Luke's/Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, 1111 Amsterdam Avenue, New York, New York 10025, USA.
Blandine
B
Laferrère
Cynthia
C
Abraham
Marianne
M
Awad
Stephanie
S
Jean-Baptiste
Allison B
AB
Hart
Pilar
P
Garcia-Lorda
Peter
P
Kokkoris
Colleen D
CD
Russell
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D020738:Leptin / Q000097:blood*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology*
D007328:Insulin; D020738:Leptin; D006854:Hydrocortisone; D008797:Metyrapone