Obestatin is a hormone that is produced in specialized epithelial cells of the stomach and small intestine of several animals including humans. Obestatin was originally identified as an

anorectic An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek ''ἀν-'' (an-) = "without" a ...

peptide, but its effect on food intake remains controversial.

Discovery

Obestatin was discovered using a

bioinformatics Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...

approach: by computer search of the sequenced genomes of several organisms. *

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.

Gene and transcription

Obestatin is encoded by the same gene that encodes

ghrelin Ghrelin (; or lenomorelin, INN) is a hormone produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highe ...

, a peptide hormone. The mRNA produced from the ''GHRL'' gene has four exons. Five products of similar structure and function arise: the first is the 117-amino acid ''preproghrelin''. (It is homologous to promotilin; both are members of the

motilin Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the ''MLN'' gene. Motilin is secreted by endocrine Mo cells (also referred to as M cells, which are not the same as the M cells, or microfold c ...

family). It is cleaved to produce ''proghrelin'' which is cleaved to produce a 28-amino acid ''ghrelin'' (unacylated) and ''C-ghrelin''(acylated). ''Obestatin'' is presumed to be cleaved from C-ghrelin.

Receptor

It was originally proposed that

GPR39 G-protein coupled receptor 39 is a protein that in humans is encoded by the ''GPR39'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation ...

functioned as an obestatin receptor, however more recent findings suggest that this is unlikely.

Blood levels

As yet no biochemical studies of circulating obestatin have been carried out.

Function

Obestatin opposes the actions of ghrelin which are growth hormone secretion and increased appetite. The purpose of producing two hormones with opposing effects is not clear: removing the ghrelin gene from mice did not significantly reduce food intake. 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. Obestatin has opposite action to ghrelin on food intake and plays a role in energy balance. Circuit-resistance exercise resulted in a significant change in GH levels, but had no effect on plasma Obestatin levels.

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 Prader–Willi syndrome (PWS) is a genetic disorder caused by a loss of function of specific genes on chromosome 15. In newborns, symptoms include weak muscles, poor feeding, and slow development. Beginning in childhood, those affected become c ...

, and type II diabetes mellitus.

References

External links

* {{MeshName, obestatin, human Peptide hormones Obesity