A new study offers evidence against the long-standing belief that the gut hormone ghrelin stimulates hunger.
Researchers now show that that the hormone enhances fat buildup without affecting appetite in rodents. The findings may explain why anti-obesity treatments targeting ghrelin have largely failed to curb appetite, suggesting that these drugs' benefits may lie in reducing body fat instead.
Ghrelin, commonly known as a "hunger hormone" secreted when the stomach is empty, has long been linked to food-seeking behaviors. However, studies have yielded inconsistent results on the effects of ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), on food intake. This puzzling variation may be due to the fact that the receptor can signal both with and without ghrelin, complicating efforts to tease apart GHSR signaling triggered specifically by ghrelin.
To better dissect ghrelin's effects, Yacine Chebani and colleagues studied r ats carrying a GHSR mutation that enhanced the receptor's sensitivity to ghrelin. (Rats, unlike mice, allow for frequent blood draws while being conscious.) When fed a normal diet, these rats ate no more food than their normal counterparts. Nonetheless, rats more sensitive to ghrelin gained more weight and body fat and developed insulin resistance.
These findings suggest that ghrelin may regulate fat storage instead of appetite, a new understanding that could help design anti-obesity drugs to more efficiently target ghrelin. A related Focus by Roy Smith discusses the findings in more detail.