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Submitted on August 25, 2003
Accepted on January 13, 2004
The Center for Vaccine Development (S.V.A.), the Obesity and Diabetes Research Center (G.A., B.C.H.), the Division of Endocrinology, Diabetes, and Nutrition (N.G., M.J.G.), University of Maryland School of Medicine, Baltimore, Maryland 21201 and the National Institute on Alcohol Abuse and Alcoholism, Laboratory of Clinical Studies-Primate Section Unit (D.H.), National Institute of Child Health and Human Development, Laboratory of Comparative Ethology (S.S.), National Institutes of Health, Poolesville, Maryland 20837
* To whom correspondence should be addressed. E-mail: sangelon{at}medicine.umaryland.edu.
Ghrelin stimulates release of growth hormone from the pituitary, stimulates appetite, and may influence metabolic processes in other tissues expressing the growth hormone secretagogue receptor. Ghrelin can thus influence behaviors and endocrine pathways contributing to weight gain. In this study we characterized the ghrelin gene from the rhesus monkey and analyzed the association of plasma ghrelin levels with metabolic and endocrine markers. Rhesus ghrelin is 97%, 91% and 96% homologous to the human cDNA, gene and peptide, respectively. Ghrelin expression was highest in the stomach with lower levels found in muscle and duodenum. In these tissues, ghrelin expression in calorie restricted and obese animals was about 40% to 99% lower than in lean animals. In addition, ghrelin expression in muscle was fairly high and may allow this tissue to contribute significantly to plasma levels. Fasting plasma ghrelin concentrations were also inversely correlated with BMI and exhibited a non-linear association with age with increased levels in younger and older monkeys and lower levels in middle-aged monkeys. While a significant inverse correlation between fasting plasma ghrelin and fasting insulin levels were found, intravenous glucose and insulin administration did not significantly alter ghrelin levels. These studies demonstrate that ghrelin levels are influenced by age related factors and adiposity in the rhesus monkey. These similarities between the rhesus monkey and human ghrelin genes and plasma ghrelin responses suggest a unique opportunity to study the mechanisms regulating ghrelin secretion and gene expression in different tissues in normal and disease states using this model system.
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