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We were interested to read the article of Asakawa et al (Gut 2005;54:18–24) which reported that intracerebroventricular and peripheral administration of desacylated ghrelin inhibited food intake in mice in the fasted state. Acylated ghrelin (AG) has a unique biological structure with an acyl side chain on the third amino acid residue. AG is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a)1 and stimulates feeding and growth hormone release. In contrast, desacylated ghrelin (DAG), which does not have the acyl side chain, has no affinity for the GHS-R1a.1 As the authors suggest, their results might indicate the presence of an alternative receptor through which desacylated ghrelin acts.
We were interested in investigating whether DAG would modulate feeding. We injected saline, 0.3 nmol/g AG, and 0.3 nmol/g DAG into C57Bl6 male mice intraperitoneally on two occasions, firstly in the fed state and secondly following a 20 hour fast, and measured food intake at 1, 2, 4, 6, and 24 hours post injection (fig 1). In the fasting experiment, we also injected 0.03 nmol/g PYY3–36 as a positive control. All animal procedures were approved by the British Home Office Animals (Scientific Procedures) Act 1986 (project license No 70/5281). Results were analysed using a one way repeated measures ANOVA. As previously reported,2 AG stimulated feeding in the fed state. However, DAG had no significant effect on food intake in the fed state. In the fasting study, PYY3–36 significantly inhibited feeding. AG stimulated cumulative food intake in fasted mice for up to six hours post injection although the percentage increase compared with saline was less than in the fed state (per cent increase two hours following ghrelin injection: fed state 320%, fasted state 30%). In contrast with the findings of Asakawa et al, DAG had no effect on food intake at any time point examined. We used a higher dose of DAG than that administered by Asakawa et al (approximately 7.5 nmol v 3 nmol per mouse) and therefore the absence of a feeding effect associated with DAG is unlikely to be explained by differences in dosing.
In conclusion, we have observed that acylated ghrelin stimulated food intake in the fasting as well as in the fed state. In contrast with the findings of Asakawa et al, there was no alteration in feeding in either the fed or fasting state following desacylated ghrelin. Our results suggest that circulating acylated ghrelin stimulates feeding independently of desacylated ghrelin.
We thank the Wellcome Trust for programme grant support and for clinical training fellowships for NMN and MRD.
Conflict of interest: None declared.
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