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Circulating acylated ghrelin level decreases in accordance with the extent of atrophic gastritis

  • Original Article—Alimentary Tract
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Abstract

Purpose

We attempted to clarify the significance of atrophic change of gastric mucosa for reduction of plasma ghrelin concentration irrespective of Helicobacter pylori (Hp) infection.

Methods

Plasma acylated (acyl-)ghrelin concentration in 220 subjects, both with and without atrophic gastritis, was measured with an enzyme immunoassay kit. The extent of atrophic change of gastric mucosa was assessed and graded endoscopically. Hp infection was determined by assay of the anti-Hp antibody with an ELISA assay kit.

Results

Plasma acyl-ghrelin concentration was significantly lower in the Hp positive than the Hp negative group, and Hp eradication significantly increased plasma acyl-ghrelin concentrations in Hp positive subjects. Plasma acyl-ghrelin was significantly lower in subjects with severely atrophic gastritis than in those with mild or moderate atrophic gastritis, irrespective of Hp infection or age group (<60 years old or ≧60 years old). In male subjects with a normal body mass index, plasma acyl-ghrelin concentrations in subjects with severely atrophic gastritis were significantly lower than those in subjects with mildly or moderately atrophic gastritis, suggesting that the results of the study are independent of emaciation or obesity. Logistic regression analysis showed that gastric atrophy is the key factor that modulates plasma acyl-ghrelin levels.

Conclusions

The results suggest that plasma acyl-ghrelin concentration decreases in accordance with the extent of atrophic change in gastric mucosa irrespective of Hp infection, indicating that the low plasma acyl-ghrelin level of subjects with Hp infection is mainly caused by the progress of atrophic changes in gastric mucosa.

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References

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a novel growth hormone releasing acylated peptide from stomach. Nature. 1999;402:656–60.

    Article  PubMed  CAS  Google Scholar 

  2. Date Y, Kojima Y, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, et al. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology. 2000;141:4255–61.

    Article  PubMed  CAS  Google Scholar 

  3. Tscop M, Smiley DL, Heiman M. Ghrelin induces adiposity in rodents. Nature. 2000;407:908–13.

    Article  Google Scholar 

  4. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 2000;141:4325–8.

    Article  PubMed  CAS  Google Scholar 

  5. Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I. Central effect of ghrelin, an endogenous growth hormone secretagogue, on hypothalamic peptide gene expression. Endocrinology. 2000;141:4797–800.

    Article  PubMed  CAS  Google Scholar 

  6. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194–8.

    Article  PubMed  CAS  Google Scholar 

  7. Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, et al. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology. 2001;120:337–45.

    Article  PubMed  CAS  Google Scholar 

  8. Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes. 2001;50:227–32.

    Article  PubMed  CAS  Google Scholar 

  9. Wren AM, Seal LA, Cohen MA, Brynes AE, Frost GS, Murphy KG, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86:5992–5.

    Article  PubMed  CAS  Google Scholar 

  10. Masuda Y, Tanaka T, Inomata M, Ohnuma N, Tanaka S, Itoh Z, et al. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun. 2000;276:905–8.

    Article  PubMed  CAS  Google Scholar 

  11. 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;280:904–7.

    Article  PubMed  CAS  Google Scholar 

  12. Yakabi K, Shoki R, Onouchi T, Tanaka T, Ohno S, Miura S, et al. Histamine mediates the stimulatory action of ghrelin on acid secretion in rat stomach. Dig Dis Sci. 2006;56:1313–21.

    Article  CAS  Google Scholar 

  13. 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;50:1714–9.

    Article  PubMed  CAS  Google Scholar 

  14. Nwokolo CU, Freshwater DA, O’Hare P, Randeva HS. Plasma ghrelin following cure of Helicobacter pylori. Gut. 2003;52:637–40.

    Article  PubMed  CAS  Google Scholar 

  15. Isomoto H, Nakazato M, Ueno H, Date y, Nishi Y, Mukae H, et al. Low plasma ghrelin levels in patients with Helicobacter pylori-associated gastritis. Am J Med. 2004;117:429–32.

    Article  PubMed  CAS  Google Scholar 

  16. Tatsuguchi A, Miyake K, Gudis K, Futagami S, Tsukui T, Wada K, et al. Effect of Helicobacter pylori infection on ghrelin expression in human gastric mucosa. Am J Gastroenterol. 2004;99:2121–7.

    Article  PubMed  CAS  Google Scholar 

  17. Osawa H, Nakazato M, Date Y, Kita H, Ohnishi H, Ueno H, et al. Impaired production of gastric ghrelin in chronic gastritis associated with Helicobacter pylori. J Clin Endocrinol Metab. 2005;90:10–6.

    Article  PubMed  CAS  Google Scholar 

  18. Suzuki H, Masaoka T, Hosoda H, Nomura S, Ohara T, Kangawa K, et al. Plasma ghrelin concentration correlates with the levels of serum pepsinogen I, and pepsinogen I/II ratio—a possible novel and non-invasive marker for gastric atrophy. Hepatogastroenterology. 2004;51:1249–54.

    PubMed  CAS  Google Scholar 

  19. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, et al. Stomach is a main source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab. 2001;86:4753–8.

    Article  PubMed  CAS  Google Scholar 

  20. Asakawa A, Inui A, Fujimiya M, Sakamaki R, Shinhuku N, Ueta Y, et al. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin. Gut. 2005;54:8–24.

    Article  CAS  Google Scholar 

  21. Chen C, Inui A, Asakawa A, Fujino K, Kato I, Chen C, et al. Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology. 2005;129:8–25.

    Article  PubMed  CAS  Google Scholar 

  22. Yakabi K, Kawashima J, Ono S, Ochiai M, Sakurada T, Kato S, et al. The effects of acylated ghrelin and desacyl ghrelin on acid secretion and histamine production in rat stomach. Gut suppl III. 2007;59:A235.

    Google Scholar 

  23. Kimura K, Takemoto T. An endoscopic recognition of the atrophic border and its significance in chronic gastritis. Endoscopy. 1969;13:87–97.

    Article  Google Scholar 

  24. Dixon MF, Genta RM, Yardly JF, Correa P, the participants in the International Workshop on the Histopathology of Gastritis. The up-dated Sydney systems. Am J Sung Pathol. 1996;20:1161–81.

    Article  CAS  Google Scholar 

  25. Shindler R, Ortmayer P. Classification of chronic gastritis with special reference to the gastroscopic method. Arch Intern Med. 1936;57:959–78.

    Google Scholar 

  26. Akamizu T, Murayama T, Teramukai T, Miura K, Bando I, Irako T, et al. Plasma ghrelin levels in healthy elderly volunteers: the levels of acylated ghrelin in elderly females correlate positively with serum IGF-1 levels and bowel movement frequency and negatively with systolic blood pressure. J Endocrinol. 2006;188:333–44.

    Article  PubMed  CAS  Google Scholar 

  27. Haqq AM, Farooqi IS, O’Rahilly S, Stadler DD, Rosenfeld RG, Pratt KL, et al. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader- Willi syndrome. J Clin Endocrinol Metab. 2003;88:174–8.

    Article  PubMed  CAS  Google Scholar 

  28. Tshop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50:707–9.

    Article  Google Scholar 

  29. Satoh K, Kimura K, Taniguchi Y, Yoshida Y, Kihira K, Takimoto T, et al. Distribution of inflammation and atrophy in the stomach of Helicobacter pylori-positive and negative patients with chronic gastritis. Am J Gastroenterol. 1996;91:963–9.

    PubMed  CAS  Google Scholar 

  30. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N J Med. 2002;346:1623–30.

    Article  Google Scholar 

  31. Hansen TK, Dall R, Hosoda H, Kojima M, Kangawa K, Christiansen JS, et al. Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol. 2002;56:203–6.

    Article  CAS  Google Scholar 

  32. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002;87:240–4.

    Article  PubMed  CAS  Google Scholar 

  33. Geloneze B, Tambascia MA, Pilla VF, Geloneze SR, Repetto EM, Pareja JC. Ghrelin: a gut-brain hormone: effect of gastric bypass surgery. Obesity Surg. 2003;13:17–22.

    Article  Google Scholar 

  34. Gokcel A, Gumurdulu Y, Kayaselcuk F, Serin E, Ozer B, Ozsahin AK, et al. Helicobacter pylori has no effect on plasma ghrelin levels. Eur J Endocrinol. 2003;148:423–6.

    Article  PubMed  CAS  Google Scholar 

  35. Checci S, Montanaro M, Pasqui L, Ciuoli C, Cevenini C, Sestini F, et al. Serum ghrelin as a marker of atrophic body gastritis in patients with parietal cell antibodies. J Clin Endocrinol Metab. 2007;92:4346–51.

    Article  CAS  Google Scholar 

  36. Rohrea GV, Welsh JD. Correlative study: gastric secretion and histology. Gastroenterology. 1967;52:185–91.

    Google Scholar 

  37. Tatsuta M, Iishi H, Okuda S. Gastric emptying and gastrointestinal symptoms in patients with atrophic gastritis and the effects of domperidone. Scand J Gastroenterol. 1989;24:251–6.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda Tsujido-Machi, Kawagoe, Saitama, 350-8550, Japan

    Junichi Kawashima, Shino Ohno, Tomoya Sakurada, Hidehiko Takabayashi, Mitsuko Kudo, Shingo Kato & Koji Yakabi

  2. Central Research Laboratories, Teikyo University Chiba Medical Center, Ichihara, Chiba, Japan

    Shoki Ro

Authors
  1. Junichi Kawashima
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  2. Shino Ohno
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  3. Tomoya Sakurada
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  4. Hidehiko Takabayashi
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  5. Mitsuko Kudo
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  6. Shoki Ro
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  7. Shingo Kato
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  8. Koji Yakabi
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Correspondence to Junichi Kawashima.

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Kawashima, J., Ohno, S., Sakurada, T. et al. Circulating acylated ghrelin level decreases in accordance with the extent of atrophic gastritis. J Gastroenterol 44, 1046–1054 (2009). https://doi.org/10.1007/s00535-009-0120-0

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  • DOI: https://doi.org/10.1007/s00535-009-0120-0

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