Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor

被引:330
作者
Thompson, NM
Gill, DAS
Davies, R
Loveridge, N
Houston, PA
Robinson, ICAF
Wells, T
机构
[1] Cardiff Univ, Sch Biosci, Cardiff CF10 3US, S Glam, Wales
[2] Univ Cambridge, Addenbrookes Hosp, Dept Med, MRC,Bone Res Grp, Cambridge CB2 2QQ, England
[3] Hammersmith Hosp, Imperial Coll London, Dept Neuroendocrinol, Div Neurosci & Psychol Med, London W12 0NN, England
[4] Natl Inst Med Res, Div Mol Neuroendocrinol, London NW7 1AA, England
关键词
D O I
10.1210/en.2003-0899
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Ghrelin promotes fat accumulation, despite potent stimulation of the lipolytic hormone, GH. The function of the major circulating isoform of ghrelin, des-octanoyl ghrelin, is unclear, because it does not activate the GH secretagogue receptor (GHS-R-1a) and lacks the endocrine activities of ghrelin. We have now addressed these issues by infusing ghrelin, desoctanoyl ghrelin, or synthetic GHS-R-1a agonists into three rat models with moderate, severe, or total GH deficiency. We show that in the context of significant GH secretion, the adipogenic effect of systemic ghrelin infusion is pattern dependent. However, this adipogenic action is not mediated by the pituitary hormones. Using a novel unilateral local infusion adipogenesis in vivo by a direct peripheral action. Surprisingly, this effect was also observed with des-octanoyl ghrelin, whereas a potent synthetic GHS-R-1a agonist was ineffective. Thus, these adipogenic effects are mediated by a receptor other than GHS-R-1a. This is the first in vivo demonstration of a direct adipogenic effect of des-octanoyl ghrelin, a major circulating form of ghrelin that lacks GH-releasing activity. We suggest that the ratio of ghrelin and des-octanoyl ghrelin production could help regulate the balance between adipogenesis and lipolysis in response to nutritional status.
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页码:234 / 242
页数:9
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