Digestive Diseases and Sciences

, Volume 52, Issue 10, pp 2866–2872 | Cite as

Correlation Between Gastrointestinal Symptoms and Gastric Leptin and Ghrelin Expression in Patients with Gastritis

  • Dae Won Jun
  • Oh Young Lee
  • Young Yul Lee
  • Ho Soon Choi
  • Tae Hwa Kim
  • Byung Chul Yoon
Original Paper

Abstract

The purpose of this study was to examine the changes in gastric ghrelin and leptin with respect to Helicobacter pylori infection and whether such changes affect the plasma levels of leptin and ghrelin. In addition, we examined the relationship between changes in gastric mucosal ghrelin and leptin levels and gastrointestinal symptoms. Sixty-three patients diagnosed with chronic gastritis were enrolled in the study. Twenty-nine patients were Helicobacter pylori negative and 34 were Helicobacter pylori positive. Expression of ghrelin and leptin mRNA in the gastric mucosa was measured using endoscopic biopsies from the fundus. Plasma levels of ghrelin and leptin were measured by radioimmunoassay. Expression of leptin mRNA in the gastric mucosa was significantly higher in Helicobacter pylori-positive patients than in negative patients (0.38 ± 0.17 vs. 0.24 ± 0.12, p = 0.039). The expression of ghrelin was lower in positive patients than in the negative group, although this difference was not significant (p = 0.07). However, there was no significant difference in plasma leptin and ghrelin levels. Gastric mucosal ghrelin mRNA expression was significantly lower in patients with dyspepsia than in those without (0.15 ± 0.11 vs. 0.23 ± 0.20, p = 0.05). Helicobacter pylori infection and gastrointestinal symptoms could be associated with leptin and ghrelin expression in the gastric mucosa.

Keywords

Ghrelin Leptin Helicobacter pylori 

References

  1. 1.
    Date Y, Nakazato M, Murakami N, Kojima M, Kangawa K, Matsukura S (2001) Ghrelin acts in the central nervous system to stimulate gastric acid secretion. Biochem Biophys Res Commun 280:904–907PubMedCrossRefGoogle Scholar
  2. 2.
    Masuda Y, Tanaka T, Inomata N, Ohnuma N, Tanaka S, Itoh Z, Hosoda H, Kojima M, Kangawa K (2000) Ghrelin stimulates gastric acid secretion and motility in rats. Biochem Biophys Res Commun 276:905–908PubMedCrossRefGoogle Scholar
  3. 3.
    Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346:1623–1630PubMedCrossRefGoogle Scholar
  4. 4.
    Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660PubMedCrossRefGoogle Scholar
  5. 5.
    Date Y, Kojima M, Hosoda H, Sawaguchi A, Mondal MS, Suganuma T, Matsukura S, Kangawa K, Nakazato M (2000) 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 141:4255–4261PubMedCrossRefGoogle Scholar
  6. 6.
    Nwokolo CU, Freshwater DA, O’Hare P, Randeva HS (2003) Plasma ghrelin following cure of Helicobacter pylori. Gut 52:637–640PubMedCrossRefGoogle Scholar
  7. 7.
    Azuma T, Suto H, Ito Y, Muramatsu A, Ohtani M, Dojo M, Yamazaki Y, Kuriyama M, Kato T (2002) Eradication of Helicobacter pylori infection induces an increase in body mass index. Aliment Pharmacol Ther 16(Suppl 2):240–244PubMedCrossRefGoogle Scholar
  8. 8.
    Gokcel A, Gumurdulu Y, Kayaselcuk F, Serin E, Ozer B, Ozsahin AK, Guvener N (2003) Helicobacter pylori has no effect on plasma ghrelin levels. Eur J Endocrinol 148:423–426PubMedCrossRefGoogle Scholar
  9. 9.
    Murray CD, Kamm MA, Bloom SR, Emmanuel AV (2003) Ghrelin for the gastroenterologist: history and potential. Gastroenterology 125:1492–1502PubMedCrossRefGoogle Scholar
  10. 10.
    St-Pierre DH, Wang L, Tache Y (2003) Ghrelin: a novel player in the gut-brain regulation of growth hormone and energy balance. News Physiol Sci 18:242–246PubMedGoogle Scholar
  11. 11.
    Noach LA, Bosma NB, Jansen J, Hoek FJ, van Deventer SJ, Tytgat GN (1994) Mucosal tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 production in patients with Helicobacter pylori infection. Scand J Gastroenterol 29:425–429PubMedGoogle Scholar
  12. 12.
    Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N, Makino S, Fujimiya M, Niijima A, Fujino MA, Kasuga M (2001) Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 120:337–345PubMedCrossRefGoogle Scholar
  13. 13.
    Basa NR, Wang L, Arteaga JR, Heber D, Livingston EH, Tache Y (2003) Bacterial lipopolysaccharide shifts fasted plasma ghrelin to postprandial levels in rats. Neurosci Lett 343:25–28PubMedCrossRefGoogle Scholar
  14. 14.
    Peterson WL (1996) Gastrin and acid in relation to Helicobacter pylori. Aliment Pharmacol Ther 10(Suppl 1):97–102PubMedGoogle Scholar
  15. 15.
    Prewett EJ, Smith JT, Nwokolo CU, Hudson M, Sawyer AM, Pounder RE (1991) Eradication of Helicobacter pylori abolishes 24-hour hypergastrinaemia: a prospective study in healthy subjects. Aliment Pharmacol Ther 5:283–290PubMedCrossRefGoogle Scholar
  16. 16.
    Smith JT, Pounder RE, Nwokolo CU, Lanzon-Miller S, Evans DG, Graham DY, Evans DJ Jr (1990) Inappropriate hypergastrinaemia in asymptomatic healthy subjects infected with Helicobacter pylori. Gut 31:522–525PubMedGoogle Scholar
  17. 17.
    Witteman EM, Verhulst ML, de Koning RW, Hopman WP, Jansen JB (19940 Basal serum gastrin concentrations before and after eradication of Helicobacter pylori infection measured by sequence specific radioimmunoassays. Aliment Pharmacol Ther 8:515–519Google Scholar
  18. 18.
    Isomoto H, Ueno H, Nishi Y, Wen CY, Nakazato M, Kohno S (2005) Impact of Helicobacter pylori infection on ghrelin and various neuroendocrine hormones in plasma. World J Gastroenterol 11:1644–1648PubMedGoogle Scholar
  19. 19.
    Isomoto H, Ueno H, Saenko VA, Mondal MS, Nishi Y, Kawano N, Ohnita K, Mizuta Y, Ohtsuru A, Yamashita S, Nakazato M, Kohno S (2005) Impact of Helicobacter pylori infection on gastric and plasma ghrelin dynamics in humans. Am J Gastroenterol 100:1711–1720PubMedCrossRefGoogle Scholar
  20. 20.
    Nishi Y, Isomoto H, Uotani S, Wen CY, Shikuwa S, Ohnita K, Mizuta Y, Kawaguchi A, Inoue K, Kohno S (2005) Enhanced production of leptin in gastric fundic mucosa with Helicobacter pylori infection. World J Gastroenterol 11:695–699PubMedGoogle Scholar
  21. 21.
    Osawa H, Nakazato M, Date Y, Kita H, Ohnishi H, Ueno H, Shiiya T, Satoh K, Ishino Y, Sugano K (2005) Impaired production of gastric ghrelin in chronic gastritis associated with Helicobacter pylori. J Clin Endocrinol Metab 90:10–16PubMedCrossRefGoogle Scholar
  22. 22.
    Shinomiya T, Fukunaga M, Akamizu T, Irako T, Yokode M, Kangawa K, Nakai Y, Nakai Y (2005) Plasma acylated ghrelin levels correlate with subjective symptoms of functional dyspepsia in female patients. Scand J Gastroenterol 40:648–653PubMedCrossRefGoogle Scholar
  23. 23.
    Mori K, Yoshimoto A, Takaya K, Hosoda K, Ariyasu H, Yahata K, Mukoyama M, Sugawara A, Hosoda H, Kojima M, Kangawa K, Nakao K (2000) Kidney produces a novel acylated peptide, ghrelin. FEBS Lett 486:213–216PubMedCrossRefGoogle Scholar
  24. 24.
    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 (2001) Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 86:4753–4758PubMedCrossRefGoogle Scholar
  25. 25.
    Katsuki A, Urakawa H, Gabazza EC, Murashima S, Nakatani K, Togashi K, Yano Y, Adachi Y, Sumida Y (2004) Circulating level of active ghrelin is associated with abdominal adiposity, hyperinsulinemia and insulin resistance in patients with type 2 diabetes mellitus. Eur J Endocrinol 151:573–577PubMedCrossRefGoogle Scholar
  26. 26.
    McLaughlin T, Abbasi F, Lamendola C, Frayo RS, Cummings DE (2004) Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 89:1630–1635PubMedCrossRefGoogle Scholar
  27. 27.
    Sibilia V, Pagani F, Guidobono F, Locatelli V, Torsello A, Deghenghi R, Netti C (2002) Evidence for a central inhibitory role of growth hormone secretagogues and ghrelin on gastric acid secretion in conscious rats. Neuroendocrinology 75:92–97PubMedCrossRefGoogle Scholar
  28. 28.
    Broglio F, Gottero C, Prodam F, Gauna C, Muccioli G, Papotti M, Abribat T, Van Der Lely AJ, Ghigo E (2004) Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab 89:3062–3065PubMedCrossRefGoogle Scholar
  29. 29.
    Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:5992PubMedCrossRefGoogle Scholar
  30. 30.
    Broglio F, Gottero C, Prodam F, Gauna C, Muccioli G, Papotti M, Abribat T, Van Der Lely AJ, Ghigo E (2004) Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab 89:3062–3065PubMedCrossRefGoogle Scholar
  31. 31.
    Thompson NM, Gill DA, Davies R, Loveridge N, Houston PA, Robinson IC, Wells T (2004) Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 145:234–242PubMedCrossRefGoogle Scholar
  32. 32.
    Groschl M, Uhr M, Kraus T (2004) Evaluation of the comparability of commercial ghrelin assays. Clin Chem 50:457–458PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Dae Won Jun
    • 1
  • Oh Young Lee
    • 1
  • Young Yul Lee
    • 1
  • Ho Soon Choi
    • 1
  • Tae Hwa Kim
    • 1
  • Byung Chul Yoon
    • 1
  1. 1.Department of Internal MedicineHanyang University HospitalSeoulRepublic of Korea

Personalised recommendations