Enhanced responsiveness of Ghsr Q343X rats to ghrelin results in enhanced adiposity without increased appetite.

Rats carrying the Ghsr(Q343X) mutation exhibited enhanced G protein-dependent signaling in response to ghrelin, leading to increased adiposity and body weight without increased food intake. These rats also showed improved body weight stability during caloric restriction and impaired glucose tolerance under normal conditions.

The study used genetically modified rats with the Ghsr(Q343X) mutation affecting receptor signaling. Researchers assessed receptor signaling in cells and measured physiological responses in rats, including body weight, fat accumulation, glucose tolerance, and response to ghrelin or GHSR agonists.

Understanding how specific receptor mutations affect ghrelin signaling can help identify new targets for obesity and metabolic disorder treatments by modulating fat accumulation independently of appetite.

The study does not specify long-term metabolic outcomes or effects in humans, and the exact mechanisms linking receptor signaling changes to glucose intolerance require further investigation.