Should We Consider Des-acyl Ghrelin As a Separate Hormone and if So, What Does It Do?

The peptides ghrelin (or acyl ghrelin; AG), des-acyl ghrelin (DAG) and obestatin are all encoded by the prepro-ghrelin gene that is expressed predominantly in the stomach. Compared with ghrelin and obestatin, DAG has not received a great amount of attention. DAG has long been considered an inert degradation product of AG. Recent evidence, however, indicates that DAG behaves like a separate hormone. Therefore, it is believed that DAG must activate its own receptor, and that it may also interact with AG at this receptor. DAG can act together with AG, can antagonize AG and seems to have AG-independent effects. Of potential clinical importance is that an increasing number of studies suggest that DAG is a functional inhibitor of AG. Therefore, DAG or DAG analogs are being trialed in early clinical studies for treatment of metabolic disorders such as diabetes, obesity and Prader-Willi syndrome.