Deletion of Ghrelin Impairs neither Growth nor Appetite
-
Published:2003-11-15
Issue:22
Volume:23
Page:7973-7981
-
ISSN:0270-7306
-
Container-title:Molecular and Cellular Biology
-
language:en
-
Short-container-title:Mol Cell Biol
Author:
Sun Yuxiang1, Ahmed Saira1, Smith Roy G.1
Affiliation:
1. Huffington Center on Aging, Department of Molecular and Cellular Biology, and Department of Medicine, Baylor College of Medicine, Houston, Texas 77030
Abstract
ABSTRACT
Pharmacological studies show that ghrelin stimulates growth hormone release, appetite, and fat deposition, but ghrelin's physiological role in energy homeostasis has not been established. Ghrelin was also proposed to regulate leptin and insulin release and to be important for the normal function of stomach, heart, kidney, lung, testis, and placenta. To help determine a definable physiological role for ghrelin, we generated
ghrelin
-null mice. In contrast to predictions made from the pharmacology of ghrelin,
ghrelin
-null mice are not anorexic dwarfs; their size, growth rate, food intake, body composition, reproduction, gross behavior, and tissue pathology are indistinguishable from wild-type littermates. Fasting produces identical decreases in serum leptin and insulin in null and wild-type mice. Ghrelin-null mice display normal responses to starvation and diet-induced obesity. As in wild-type mice, the administration of exogenous ghrelin stimulates appetite in null mice. Our data show that ghrelin is not critically required for viability, fertility, growth, appetite, bone density, and fat deposition and not likely to be a direct regulator of leptin and insulin. Therefore, antagonists of ghrelin are unlikely to have broad utility as antiobesity agents.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference40 articles.
1. Bagnasco, M., P. S. Kalra, and S. P. Kalra. 2002. Ghrelin and leptin pulse discharge in fed and fasted rats. Endocrinology 143 : 726-729. 2. Bailey, A. R. T., R. G. Smith, and G. Leng. 1998. The non-peptide growth hormone secretagogue, MK-0677, activates hypothalamic neurones in vivo. J. Neuroendocrinol. 10 : 111-118. 3. Beck, B., N. Musse, and A. Stricker-Krongrad. 2002. Ghrelin, macronutrient intake and dietary preferences in long-evans rats. Biochem. Biophys. Res. Commun. 292 : 1031-1035. 4. Chapman, I. M., M. A. Bach, C. Van, E., M. Farmer, D. A. Krupa, A. M. Taylor, L. M. Schilling, K. Y. Cole, E. H. Skiles, S. S. Pezzoli, M. L. Hartman, J. D. Veldhuis, G. J. Gormley, and M. O. Thorner. 1996. Stimulation of the growth hormone (GH)-insulin-like growth factor-I axis by daily oral administration of a GH secretagogue (MK-0677) in healthy elderly subjects. J. Clin. Endocrinol. Metab. 81 : 4249-4257. 5. Cowley, M., R. G. Smith, S. Diano, M. Tschop, N. Pronchuk, K. Grove, C. Strasburger, M. Bidlingmaier, M. Esterman, M. Heiman, L. Garcia-Segura, E. Nillni, P. Mendez, M. Low, P. Sotonyi, J. Friedman, H. Liu, S. Pinto, W. Colmers, R. Cone, and T. Horvath. 2003. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37 : 649-661.
Cited by
549 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|