1 protein = 2 opposing weight-control hormones

Obesity, a body mass index over 30 kg/m^2, is increasing in America and many western societies. Obesity is correlated with poor health, including diabetes and cardiovascular disease. Body weight is regulated by peptide hormones secreted from the gut and brain. Zhang and colleagues noted that ghrelin, a 28 amino acid, gut-derived peptide that stimulates appetite, is post-translationally trimmed from a larger, 117 amino acid protein. They identified in this larger protein not only a signal sequence but also a whole new, 23 amino acid peptide downstream of a potential convertase cleavage site. They named this second protein obestatin, for obesity-suppressing. They found obestatin in rat gut tissue. Whereas fasting rats had more ghrelin in their blood and fed rats had less, obestatin was stable between the groups. Injecting mice with synthetic obestatin blocked ghrelin-induced weight gains. Finally, they identified the hitherto orphan GPR39 as the G protein-coupled receptor. One gene encodes one protein that yields two antagonist peptides! This story promises to be an interesting and important example of post-translationally regulated protein expression.
Zhang et al., "Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin's Effects on Food Intake" Science 11 November 2005.