Obestatin
Encyclopedia
Obestatin is a putative hormone
that is potentially produced in the cells lining the stomach
and small intestine
of several mammal
s including human
s. Obestatin was originally identified as an anorectic
peptide, but its effect on food intake remains controversial.
in 2005 identified obestatin as a new hormone with a bioinformatics
approach by computer search of the sequenced genome
s 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.
- 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 peptide
s, 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.
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
that is potentially produced in the cells lining the stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
and small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
of several mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s including human
Human
Humans are the only living species in the Homo genus...
s. Obestatin was originally identified as an anorectic
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
peptide, but its effect on food intake remains controversial.
Discovery
Research carried out at the Stanford University School of MedicineStanford University School of Medicine
Stanford University School of Medicine is a leading medical school located at Stanford University Medical Center in Stanford, California. Originally based in San Francisco, California as Cooper Medical College, it is the oldest continuously running medical school in the western United States...
in 2005 identified obestatin as a new hormone with a bioinformatics
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
approach by computer search of the sequenced genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
s 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 hormonePeptide hormone
Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...
- a relatively small protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. It is encoded by the same gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
that also encodes ghrelin
Ghrelin
Ghrelin is a 28 amino acid peptide and hormone that is produced mainly by P/D1 cells lining the fundus of the human stomach and epsilon cells of the pancreas that stimulates hunger. Ghrelin levels increase before meals and decrease after meals. It is considered the counterpart of the hormone...
, a peptide hormone that increases appetite. The protein produced by that gene breaks into two smaller peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s, 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
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
secretion and food intake induced by ghrelin. It was originally proposed that GPR39
GPR39
G-protein coupled receptor 39 is a protein that in humans is encoded by the GPR39 gene.-Further reading:...
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.Further reading
- Obestatin, A New Physiological Opponent of Ghrelin, PHOENIX PHARMACEUTICALS, INC.