Endocrine Abstracts

Background and aims: Ghrelin is the only known peripheral hormone, which increases food intake. It is released from the stomach and is thought to function as a meal initiator and signal of energy deficit. We used bacterial artificial chromosome transgenesis to generate a mouse model with increased ghrelin expression and production in stomach and brain. These mice exhibited increased circulating bioactive ghrelin and as expected were hyperphagic and glucose intolerant. We hypothesised that exposure to a high fat diet would exacerbate this phenotype.

Methods: We investigated the effect of high fat feeding on energy and glucose homeostasis in these mice. Subsequently, we determined dietary preference, expression of hypothalamic neuropeptides known to control food intake and using FPLC the circulating forms of ghrelin present under both feeding paradigms. Finally we measured food intake during continuous administration of ghrelin in wild type mice fed either regular chow (RC) or high fat diet (HFD).

Results: Firstly, we found our mice were resistant to diet induced obesity due to a significant reduction in food intake. This was not caused by alterations to food preference, hypothalamic signalling of neuropeptides known to control food intake or an alteration in the form of circulating acylated ghrelin. Secondly, we found long-term administration of ghrelin to wild type mice failed to increase ingestion of a HFD but as expected increased food intake on RC.

Conclusion: This is the first report that diets high in fat inhibit the hyperphagic effect of ghrelin and suggests that dietary environment is critically important in determining the function of ghrelin. This may be of importance when developing anti-obesity drugs targeting the ghrelin system.