This Article Full Text Full Text (PDF) All Versions of this Article: 91/6/2232    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laferrère, B. Articles by Russell, C. D. Search for Related Content PubMed PubMed Citation Articles by Laferrère, B. Articles by Russell, C. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HYDROCORTISONE METYRAPONE Related Collections Adrenal and Hypertension Neuroendocrinology and Pituitary Metabolism

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.

This article has been cited by other articles:

				T. Remer, T. Dimitriou, and C. Maser-Gluth Renal Net Acid Excretion and Plasma Leptin Are Associated with Potentially Bioactive Free Glucocorticoids in Healthy Lean Women J. Nutr., February 1, 2008; 138(2): 426S - 430S. [Abstract] [Full Text] [PDF]

				M.-J. Lee, Y. Wang, M. R. Ricci, S. Sullivan, C. D. Russell, and S. K. Fried Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E858 - E864. [Abstract] [Full Text] [PDF]