Proteins that stimulate and repress appetite appear to be cut from the same cloth. Stanford University biologists report that a newly discovered appetite suppressing hormone, called obestatin, is produced by posttranslational modification of a protein precursor that also gives rise to ghrelin, an appetite stimulator.1 The authors suggest this work may provide new targets for controlling obesity, as well as resolve an outstanding mystery surrounding ghrelin knockout mice.
The team, led by Aaron Hsueh at Stanford University's School of Medicine, predicted the existence of obestatin through a bioinformatic search for hormones derived from protein precursors of known peptide hormones. The exercise yielded a 23-amino-acid region of preproghrelin that is highly conserved across several mammalian species.
The authors confirmed the prediction when they isolated obestatin from rat stomach extracts and blood. Synthetic obestatin administered to rodents reduced appetite, weight gain, and the rate of gastric emptying.
Given that obestatin and ghrelin derive from the same gene, ghrelin-null mice would also lack obestatin, counterbalancing ghrelin's absence. Still, Matthias Tschöp of the Obesity Research Center at the University of Cincinnati, suggests that the relationship between ghrelin and obestatin might not be so simple. "There is too much we don't know yet," he says.