Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor.
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-R1a) and lacks the endocrine activities of ghrelin. We have now addressed these issues by infusing ghrelin, des-octanoyl ghrelin, or synthetic GHS-R1a 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 strategy, we demonstrate that ghrelin promotes bone marrow adipogenesis in vivo by a direct peripheral action. Surprisingly, this effect was also observed with des-octanoyl ghrelin, whereas a potent synthetic GHS-R1a agonist was ineffective. Thus, these adipogenic effects are mediated by a receptor other than GHS-R1a. 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.
Thompson
Nichola M
NM
School of Biosciences, Cardiff University, Cardiff, United Kingdom CF10 3US.
Gill
Dave A S
DA
Davies
Rhos
R
Loveridge
Nigel
N
Houston
Pamela A
PA
Robinson
Iain C A F
IC
Wells
Timothy
T
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D004393:Dwarfism, Pituitary / Q000378:metabolism*; D054439:Ghrelin; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D036361:Peptide Hormones / Q000378:metabolism* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D020551:Pulse Therapy, Drug; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D054440:Receptors, Ghrelin; D013141:Spiro Compounds / Q000494:pharmacology; D013977:Tibia / Q000187:drug effects
D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; D010880:Piperidines; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013141:Spiro Compounds; C102119:L 163255; C041048:growth hormone releasing hexapeptide