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This version published online on November 16, 2004
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-1124
A more recent version of this article appeared on February 1, 2005
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Submitted on June 15, 2004
Accepted on November 8, 2004

Circulating melanin-concentrating hormone (MCH), agouti-related protein (AGRP), and alpha melanocyte-stimulating hormone ({alpha}-MSH) levels in relation to body composition; alterations in response to food deprivation and recombinant human leptin administration

Alina Gavrila, Jean L. Chan, Lisa C. Miller, Kathleen Heist, Nikos Yiannakouris, and Christos S. Mantzoros*

Division of Endocrinology and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA; Department of Biostatistics, Harvard School of Public Health, Boston, MA; Dept of Nutrition and Home Economics and Ecology, Harokopio University, Athens, Greece

* To whom correspondence should be addressed.
Christos S. Mantzoros, E-mail: cmantzor{at}caregroup.harvard.edu

We sought to evaluate whether circulating levels of melanin-concentrating hormone (MCH), agouti-related protein (AGRP), and {alpha} melanocyte-stimulating hormone ({alpha}-MSH) could serve as useful markers of energy homeostasis in humans. We first assessed correlations of serum MCH, AGRP, and {alpha}-MSH with anthropometric, dietary, and hormonal variables in a cross-sectional study of 108 healthy humans. We then performed interventional studies to evaluate the effect of fasting and/or leptin administration. In 8 healthy normal-weight men, we measured serum MCH, AGRP, and {alpha}-MSH levels at baseline, after two days of fasting alone (a low leptin state) and two days of fasting with replacement-dose recombinant-methionyl human leptin (r-metHuLeptin) administration to normalize circulating leptin levels. In a separate group of 5 lean and 5 obese men, we measured MCH levels in response to increasing circulating leptin levels to the pharmacologic range by administration of one r-metHuLeptin dose in the fed state.

In the cross-sectional study, serum MCH levels were independently and positively associated with BMI and fat mass and were higher in women compared with men. Furthermore, in our interventional studies, fasting for two days significantly decreased leptin levels and increased serum MCH levels. Administration of replacement-dose r-metHuLeptin during fasting prevented the fasting-induced increase in MCH levels, but administration of a pharmacologic r-metHuLeptin dose in the fed state did not further alter MCH levels. Serum AGRP levels tended to change in directions similar to MCH, but this change was less pronounced and needs to be investigated in larger studies. In contrast, serum {alpha}-MSH levels did not correlate with body composition parameters, were not associated with caloric or macronutrient intake, and were not significantly affected by fasting or r-metHuLeptin administration.

These findings suggest that serum MCH, and possibly AGRP levels, could serve as useful peripheral markers of changes in energy homeostasis and, thus, merit further investigation.
Key words: MCH • {alpha}-MSH • AGRP • leptin • fasting • estradiol • fat mass




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