Virtual Medical Centre

Fatty foods, not empty stomach, fire up hunger hormone

The findings, the study's author says, turn the current model about ghrelin on its head and point to a novel stomach enzyme (GOAT) responsible for the ghrelin activation process that could be targeted in future treatments for metabolic diseases.

The laboratory study, led by Matthias Tschöp, MD, UC associate professor of psychiatry and internal medicine, is published online ahead of print 5 June 2009 in the journal Nature Medicine. 

Ghrelin is a hormone that was believed to accumulate during periods of fasting and is found in the body in high concentrations just before meals. It is dubbed the "hunger hormone" because it has been shown that administration of pharmacological doses acts in the brain to stimulate hunger and increase food intake in animal models and humans.

The ghrelin hormone is unique in that it requires acylation (the addition of a fatty acid) by a specific enzyme (ghrelin O-acyl transferase, or GOAT) for activation. Originally it was assumed that the fatty acids attached to ghrelin by GOAT were produced by the body during fasting.

The new data by Tschöp and his team suggests that the fatty acids needed for ghrelin activation actually come directly from ingested dietary fats. In a departure from an earlier model that was upheld for nearly a decade, Tschöp says, it appears that the ghrelin system is a lipid sensor in the stomach that informs the brain when calories are available – giving the green light to other calorie-consuming processes such as growing.

Tschöp and his team used mouse models to test the effects of over expressing the GOAT enzyme, or "knocking it out". They found that, when exposed to a lipid-rich diet, mice without GOAT accumulated less fat than normal mice, while those with over-expressed GOAT accumulated more fat mass than normal mice.