Endocrinol Metab.  2010 Dec;25(4):258-263. 10.3803/EnM.2010.25.4.258.

Ghrelin

• Park S

• KMID: 1497750
• DOI: http://doi.org/10.3803/EnM.2010.25.4.258

Abstract

No abstract available.

MeSH Terms

Ghrelin
Ghrelin

Figure

• 

  Fig. 1 From a 117-amino acid human ghrelin precursor to an active n-octanoyl modified 28-amino acid human ghrelin. After removing the signal peptide, ghrelin precursor is modified with a medium chain fatty acid, n-octanoic acid, by GOAT. This acyl-modification is essential for ghrelin's endocrine activity.

Reference

1. Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M. Ghrelin, a novel growth hormone-relasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology. 2000. 141:4255–4261.

2. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth hormone-releasing acylated peptide from stomach. Nature. 1999. 402:656–660.

3. Kojima M, Kangawa K. Structure and function of ghrelin. Results Probl Cell Differ. 2008. 46:89–115.

4. Hosoda H, Kojima M, Matsuo H, Kangawa K. Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun. 2000. 279:909–913.

5. Hosoda H, Kojima M, Matsuo H, Kangawa K. Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for the growth hormone secretagogue receptor. J Biol Chem. 2000. 275:21995–22000.

6. Smith RG, Van der Ploeg LH, Howard AD, Feighner SD, Cheng K, Hickey GJ, Wyvratt MJ Jr, Fisher MH, Nargund RP, Patchett AA. Peptidomimetic regulation of growth hormone secretion. Endocr Rev. 1997. 18:621–645.

7. Kanamoto N, Akamizu T, Tagami T, Hataya Y, Moriyama K, Takaya K, Hosoda H, Kojima M, Kangawa K, Nakao K. Genomic structure and characterization of the 5'-flanking region of the human ghrelin gene. Endocrinology. 2004. 145:4144–4153.

8. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes. 2001. 50:1714–1719.

9. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002. 87:240–244.

10. Gutierrez JA, Solenberg PJ, Perkins DR, Willency JA, Knierman MD, Jin Z, Witcher DR, Luo S, Onyia JE, Hale JE. Ghrelin octanoylation mediated by an orphan lipid transferase. Proc Natl Acad Sci U S A. 2008. 105:6320–6325.

11. Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell. 2008. 132:387–396.

12. Sakata I, Yang J, Lee CE, Osborne-Lawrence S, Rovinsky SA, Elmquist JK, Zigman JM. Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells. Am J Physiol Endocrinol Metab. 2009. 297:E134–E141.

13. Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, Hamelin M, Hreniuk DL, Palyha OC, Anderson J, Paress PS, Diaz C, Chou M, Liu KK, McKee KK, Pong SS, Chaung LY, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji DJ, Dean DC, Melillo DG, Patchett AA, Nargund R, Griffin PR, DeMartino JA, Gupta SK, Schaeffer JM, Smith RG, Van der Ploeg LH. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996. 273:974–977.

14. Nanzer AM, Khalaf S, Mozid AM, Fowkes RC, Patel MV, Burrin JM, Grossman AB, Korbonits M. Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway. Eur J Endocrinol. 2004. 151:233–240.

15. Kohno D, Gao HZ, Muroya S, Kikuyama S, Yada T. Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes. 2003. 52:948–956.

16. Date Y, Murakami N, Toshinai K, Matsukura S, Niijima A, Matsuo H, Kangawa K, Nakazato M. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology. 2002. 123:1120–1128.

17. Zhang W, Lin TR, Hu Y, Fan Y, Zhao L, Stuenkel EL, Mulholland MW. Ghrelin stimulates neurogenesis in the dorsal motor nucleus of the vagus. J Physiol. 2004. 559:729–737.

18. Date Y, Nakazato M, Murakami N, Kojima M, Kangawa K, Matsukura S. Ghrelin acts in the central nervous system to stimulate gastric acid secretion. Biochem Biophys Res Commun. 2001. 280:904–907.

19. Date Y, Shimbara T, Koda S, Toshinai K, Ida T, Murakami N, Miyazato M, Kokame K, Ishizuka Y, Ishida Y, Kageyama H, Shioda S, Kangawa K, Nakazato M. Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus. Cell Metab. 2006. 4:323–331.

20. Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C, Hsueh AJ. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science. 2005. 310:996–999.

21. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005. 85:495–522.

22. Sun Y, Ahmed S, Smith RG. Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol. 2003. 23:7973–7981.

23. Wortley KE, Anderson KD, Garcia K, Murray JD, Malinova L, Liu R, Moncrieffe M, Thabet K, Cox HJ, Yancopoulos GD, Wiegand SJ, Sleeman MW. Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci U S A. 2004. 101:8227–8232.

24. Erickson JC, Clegg KE, Palmiter RD. Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature. 1996. 381:415–421.

25. Qian S, Chen H, Weingarth D, Trumbauer ME, Novi DE, Guan X, Yu H, Shen Z, Feng Y, Frazier E, Chen A, Camacho RE, Shearman LP, Gopal-Truter S, MacNeil DJ, Van der Ploeg LH, Marsh DJ. Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol. 2002. 22:5027–5035.

26. Hataya Y, Akamizu T, Takaya K, Kanamoto N, Ariyasu H, Saijo M, Moriyama K, Shimatsu A, Kojima M, Kangawa K, Nakao K. A low dose of ghrelin stimulates growth hormone (GH) release synergistically with GH-releasing hormone in humans. J Clin Endocrinol Metab. 2001. 86:4552.

27. Morton GJ, Schwartz MW. The NPY/AgRP neuron and energy homeostasis. Int J Obes Relat Metab Disord. 2001. 25:S56–S62.

28. Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I. Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Diabetes. 2001. 50:2438–2443.

29. Andersson U, Filipsson K, Abbott CR, Woods A, Smith K, Bloom SR, Carling D, Small CJ. AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem. 2004. 279:12005–12008.

30. Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, Bhattacharya S, Carpenter R, Grossman AB, Korbonits M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab. 2002. 87:2988.

31. Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, Hayashi Y, Kangawa K. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol Regul Integr Comp Physiol. 2001. 280:R1483–R1487.

32. Nagaya N, Kangawa K. Ghrelin improves left ventricular dysfunction and cardiac cachexia in heart failure. Curr Opin Pharmacol. 2003. 3:146–151.

33. Masuda Y, Tanaka T, Inomata N, Ohnuma N, Tanaka S, Itoh Z, Hosoda H, Kojima M, Kangawa K. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun. 2000. 276:905–908.

34. Adeghate E, Ponery AS. Ghrelin stimulates insulin secretion from the pancreas of normal and diabetic rats. J Neuroendocrinol. 2002. 14:555–560.

35. Broglio F, Arvat E, Benso A, Gottero C, Muccioli G, Papotti M, van der Lely AJ, Deghenghi R, Ghigo E. Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab. 2001. 86:5083–5086.

36. Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, Gaskin FS, Nonaka N, Jaeger LB, Banks WA, Morley JE, Pinto S, Sherwin RS, Xu L, Yamada KA, Sleeman MW, Tschöp MH, Horvath TL. Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci. 2006. 9:381–388.

37. Ming GL, Song H. Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci. 2005. 28:223–250.

38. Nakahara K, Nakagawa M, Baba Y, Sato M, Toshinai K, Date Y, Nakazato M, Kojima M, Miyazato M, Kaiya H, Hosoda H, Kangawa K, Murakami N. Maternal ghrelin plays an important role in rat fetal development during pregnancy. Endocrinology. 2006. 147:1333–1342.

39. Sato M, Nakahara K, Goto S, Kaiya H, Miyazato M, Date Y, Nakazato M, Kangawa K, Murakami N. Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord. Biochem Biophys Res Commun. 2006. 350:598–603.

40. Zhang W, Hu Y, Lin TR, Fan Y, Mulholland MW. Stimulation of neurogenesis in rat nucleus of the solitary tract by ghrelin. Peptides. 2005. 26:2280–2288.

41. Johansson I, Destefanis S, Aberg ND, Aberg MA, Blomgren K, Zhu C, Ghè C, Granata R, Ghigo E, Muccioli G, Eriksson PS, Isgaard J. Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells. Endocrinology. 2008. 149:2191–2199.

42. Moon M, Kim S, Hwang L, Park S. Ghrelin regulates hippocampal neurogenesis in adult mice. Endocr J. 2009. 56:525–531.

43. Chung H, Kim E, Lee DH, Seo S, Ju S, Lee D, Kim H, Park S. Ghrelin inhibits apoptosis in hypothalamic neuronal cells during oxygen-glucose deprivation. Endocrinology. 2007. 148:148–159.

44. Chung H, Seo S, Moon M, Park S. Phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3 beta and ERK1/2 pathways mediate protective effects of acylated and unacylated ghrelin against oxygen-glucose deprivation-induced apoptosis in primary rat cortical neuronal cells. J Endocrinol. 2008. 198:511–521.

45. Hwang S, Moon M, Kim S, Hwang L, Ahn KJ, Park S. Neuroprotective effect of ghrelin is associated with decreased expression of prostate apoptosis response-4. Endocr J. 2009. 56:609–617.

46. Moon M, Kim HG, Hwang L, Seo JH, Kim S, Hwang S, Kim S, Lee D, Chung H, Oh MS, Lee KT, Park S. Neuroprotective effect of ghrelin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease by blocking microglial activation. Neurotox Res. 2009. 15:332–347.

47. Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001. 50:707–709.

48. Fobi MA. Surgical treatment of obesity: a review. J Natl Med Assoc. 2004. 96:61–75.

49. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002. 346:1623–1630.

50. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A, Doi K, Hosoda H, Kojima M, Kangawa K, Nakao K. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab. 2001. 86:4753–4758.

51. Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. 2002. 8:643–644.

52. Shimizu Y, Nagaya N, Isobe T, Imazu M, Okumura H, Hosoda H, Kojima M, Kangawa K, Kohno N. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res. 2003. 9:774–778.