The hyperphagic effect of ghrelin is inhibited in mice by a diet high in fat

JV Gardiner, D Campbell, M Patterson, A Kent… - Gastroenterology, 2010 - Elsevier
JV Gardiner, D Campbell, M Patterson, A Kent, MA Ghatei, SR Bloom, GA Bewick
Gastroenterology, 2010Elsevier
BACKGROUND & AIMS: Ghrelin is the only peripheral hormone known to increase food
intake. It is released from the stomach and is thought to function as a signal of energy deficit
and a meal initiator. We generated transgenic mice in which levels of bioactive ghrelin are
increased in the stomach and circulation. These mice, as expected, are hyperphagic and
glucose intolerant. We investigated whether exposure to a high-fat diet (HFD) would
exacerbate this phenotype. METHODS: We investigated the effect of HFD on energy and …
BACKGROUND & AIMS
Ghrelin is the only peripheral hormone known to increase food intake. It is released from the stomach and is thought to function as a signal of energy deficit and a meal initiator. We generated transgenic mice in which levels of bioactive ghrelin are increased in the stomach and circulation. These mice, as expected, are hyperphagic and glucose intolerant. We investigated whether exposure to a high-fat diet (HFD) would exacerbate this phenotype.
METHODS
We investigated the effect of HFD on energy and glucose homeostasis in ghrelin transgenic mice. We determined dietary preference; expression of hypothalamic neuropeptides that control food intake; and, using fast-performance liquid chromatography, the circulating forms of ghrelin. We measured food intake during continuous administration of ghrelin in wild-type mice fed either regular chow or an HFD.
RESULTS
Ghrelin transgenic mice were resistant to diet-induced obesity because of their reduced food intake. This was not caused by alterations to food preference, hypothalamic signaling of neuropeptides that control food intake, or the form of circulating acylated ghrelin. Long-term administration of ghrelin to wild-type mice failed to increase ingestion of an HFD but, as expected, increased intake of regular chow.
CONCLUSIONS
This is the first report that diets high in fat inhibit the hyperphagic effect of ghrelin; these findings indicate that features of the diet are important determinants of ghrelin's function. This information is important for the development of anti-obesity drugs that target ghrelin signaling.
Elsevier