Obestatin

Obestatin is a putative hormone that is potentially produced in the cells lining the stomach and small intestine of several mammals including humans. Obestatin was originally identified as an anorectic peptide, but its effect on food intake remains controversial.

Discovery
Research carried out at the Stanford University School of Medicine in 2005 identified obestatin as a new hormone with a bioinformatics approach by computer search of the sequenced genomes of several organisms. As yet no biochemical studies of circulating obestatin have been carried out, and no secretory convertase is capable of cleaving the recombinant proghrelin precursor by cleavage at the single basic residue required for generation of the obestatin sequence. Thus the physiological generation of this particular peptide sequence remains unproven.

Function and mechanism
Obestatin is a putative peptide hormone - a relatively small protein. It is encoded by the same gene that also encodes ghrelin, a peptide hormone that increases appetite. The protein produced by that gene breaks into two smaller peptides, ghrelin and obestatin. The purpose of this mechanism that produces two hormones with opposing effects remains unclear, however may explain earlier findings, namely that removing the ghrelin gene from mice did not significantly reduce their appetite.

Obestatin has been shown to antagonise growth hormone secretion and food intake induced by ghrelin. It was originally proposed that GPR39 functioned as an obestatin receptor, however more recent findings suggest that this is unlikely.

Clinical significance
Studies on the obestatin/ghrelin ratio in the gastrointestinal tract and plasma are associated with some diseases such as irritable bowel syndrome (IBS), obesity, Prader-Willi syndrome, and type II diabetes mellitus.

Structure
The Obestatin structure to the right was determined by NMR. The length of the polypeptide was found to be 24 residues with a secondary structure 29% helical. Specifically 2 helices and 7 residues are formed.