Obestatin

ghrelin/obestatin preprohormone

Obestatin NMR structure in SDS / DPC micellar solution.[1]
Identifiers
Symbol GHRL
Entrez 51738
HUGO 18129
OMIM 605353
RefSeq NM_016362
UniProt Q9UBU3
Other data
Locus Chr. 3 p26-p25

Obestatin is a hormone that is produced in specialized epithelial cells of the stomach and small intestine of several mammals including humans.[2] Obestatin was originally identified as an anorectic peptide, but its effect on food intake remains controversial.[3]

Discovery

Obestatin was discovered using a bioinformatics approach: by computer search of the sequenced genomes of several organisms.[4]

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.[1]

Gene and transcription

Obestatin is encoded by the same gene that encodes ghrelin, 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 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.[5]

Receptor

It was originally proposed that GPR39 functioned as an obestatin receptor, however more recent findings suggest that this is unlikely.[6]

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.[3] 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.[7] 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.[8] Circuit-resistance exercise resulted in a significant change in GH levels, but had no effect on plasma Obestatin levels.[9]

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),[10] obesity,[11] Prader–Willi syndrome,[12] and type II diabetes mellitus.[13][14]

See also

References

  1. 1 2 PDB: 2JSH​; Scrima M, Campiglia P, Esposito C, Gomez-Monterrey I, Novellino E, D'Ursi AM (November 2007). "Obestatin conformational features: a strategy to unveil obestatin's biological role?". Biochem. Biophys. Res. Commun. 363 (3): 500–5. doi:10.1016/j.bbrc.2007.08.200. PMID 17904104.
  2. ↑ Gourcerol G, St-Pierre DH, Taché Y (June 2007). "Lack of obestatin effects on food intake: should obestatin be renamed ghrelin-associated peptide (GAP)?". Regul. Pept. 141 (1–3): 1–7. doi:10.1016/j.regpep.2006.12.023. PMID 17321609.
  3. 1 2 Hassouna R, Zizzari P, Tolle V (July 2010). "The ghrelin/obestatin balance in the physiological and pathological control of growth hormone secretion, body composition and food intake". J. Neuroendocrinol. 22 (7): 793–804. doi:10.1111/j.1365-2826.2010.02019.x. PMID 20456603.
  4. ↑ Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJ (November 2005). "Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake". Science 310 (5750): 996–9. doi:10.1126/science.1117255. PMID 16284174. Lay summary – New York Times.
  5. ↑ Seim I, Amorim L, Walpole C, Carter S, Chopin LK, Herington AC (2010). "Ghrelin gene-related peptides: multifunctional endocrine / autocrine modulators in health and disease". Clin Exp Pharmacol Physiol. 37 (1): 125–31. doi:10.1111/j.1440-1681.2009.05241.x. PMID 19566830.
  6. ↑ Dong XY, He JM, Tang SQ, Li HY, Jiang QY, Zou XT (February 2009). "Is GPR39 the natural receptor of obestatin?". Peptides 30 (2): 431–8. doi:10.1016/j.peptides.2008.09.022. PMID 18977259.
  7. ↑ Ozawa A, Cai Y, Lindberg I (April 2007). "Production of bioactive peptides in an in vitro system". Anal Biochem 366 (2): 182–9. doi:10.1016/j.ab.2007.04.020. PMC 2128726. PMID 17540328.
  8. ↑ Zizzari P, Longchamps R, Epelbaum J, Bluet-Pajot MT (2007). "Obestatin partially affects ghrelin stimulation of food intake and growth hormone secretion in rodents". Endocrinology 148 (4): 1648–53. doi:10.1210/en.2006-1231. PMC 1890395. PMID 17204551.
  9. ↑ Ghanbari-Niaki A, Saghebjoo M, Rahbarizadeh F (2008). "single circuit-resistance exercise has no effect on plasma obestatin levels in female college students". Peptides 29 (3): 487–490. doi:10.1016/j.peptides.2007.11.002. PMID 18308154.
  10. ↑ Sjölund K, Ekman R, Wierup N (June 2010). "Covariation of plasma ghrelin and motilin in irritable bowel syndrome". Peptides 31 (6): 1109–12. doi:10.1016/j.peptides.2010.03.021. PMID 20338210.
  11. ↑ Zhang N, Yuan C, Li Z, Li J, Li X, Li C, Li R, Wang SR (January 2011). "Meta-analysis of the relationship between obestatin and ghrelin levels and the ghrelin/obestatin ratio with respect to obesity". Am. J. Med. Sci. 341 (1): 48–55. doi:10.1097/MAJ.0b013e3181ec41ed. PMID 21139496.
  12. ↑ Haqq AM, Muehlbauer M, Svetkey LP, Newgard CB, Purnell JQ, Grambow SC, Freemark MS (December 2007). "Altered distribution of adiponectin isoforms in children with Prader-Willi syndrome (PWS): association with insulin sensitivity and circulating satiety peptide hormones". Clin. Endocrinol. (Oxf) 67 (6): 944–51. doi:10.1111/j.1365-2265.2007.02991.x. PMC 2605973. PMID 17666087.
  13. ↑ Qi X, Li L, Yang G, Liu J, Li K, Tang Y, Liou H, Boden G (April 2007). "Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus". Clin. Endocrinol. (Oxf) 66 (4): 593–7. doi:10.1111/j.1365-2265.2007.02776.x. PMID 17371480.
  14. ↑ Harsch IA, Koebnick C, Tasi AM, Hahn EG, Konturek PC (October 2009). "Ghrelin and obestatin levels in type 2 diabetic patients with and without delayed gastric emptying". Dig. Dis. Sci. 54 (10): 2161–6. doi:10.1007/s10620-008-0622-2. PMID 19082715.

Further reading

External links

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