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Published in: World Journal of Surgery 12/2013

01-12-2013

Clinical Significance of Ghrelin Expression in the Gastric Mucosa of Morbidly Obese Patients

Authors: Yasuhiro Miyazaki, Shuji Takiguchi, Yosuke Seki, Kazunori Kasama, Tsuyoshi Takahashi, Yukinori Kurokawa, Makoto Yamasaki, Hiroshi Miyata, Kiyokazu Nakajima, Masaki Mori, Yuichiro Doki

Published in: World Journal of Surgery | Issue 12/2013

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Abstract

Background

The concentration of ghrelin, which can affect body weight by influencing appetite, is thought to decrease after sleeve gastrectomy. However, no detailed investigations have examined ghrelin expression in the stomach. The purpose of the present study was to assess localized ghrelin expression and its clinical significance in obese patients.

Methods

A total of 52 obese patients who underwent sleeve gastrectomy with or without duodenojejunal bypass were enrolled in the study. The number of ghrelin-positive cells (GPCs) was counted using immunohistochemistry of the gastric mucosa at the fundus. The obese patients were compared with 14 nonobese patients treated for gastric cancer. Ghrelin mRNA expression was also measured in 22 obese patients using a quantitative reverse transcription polymerase chain reaction.

Results

The number of GPCs was significantly higher in obese patients than in nonobese controls (33.2 ± 18.3 vs. 14.1 ± 6.1; p < 0.001) and correlated with ghrelin mRNA expression. The obese patients were divided into two groups with high and low ghrelin levels based on the number of GPCs. The percent excess body weight loss was significantly greater in the high-ghrelin group, without differences in the patient backgrounds between the two groups (p = 0.015).

Conclusions

The number of GPCs was higher in obese patients than in nonobese patients and varied individually regardless of body weight. These results suggest that ghrelin expression in gastric mucosa might be a prognostic factor after surgery.
Literature
1.
go back to reference Buchwald H, Avidor Y, Braunwald E et al (2004) Bariatric surgery: a systematic review and meta-analysis. JAMA 292:1724–1737PubMedCrossRef Buchwald H, Avidor Y, Braunwald E et al (2004) Bariatric surgery: a systematic review and meta-analysis. JAMA 292:1724–1737PubMedCrossRef
2.
go back to reference Sjostrom L, Narbro K, Sjostrom CD et al (2007) Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 357:741–752PubMedCrossRef Sjostrom L, Narbro K, Sjostrom CD et al (2007) Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 357:741–752PubMedCrossRef
3.
go back to reference Christou NV, Sampalis JS, Liberman M et al (2004) Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 240:416–423 (discussion 423–414)PubMedCrossRef Christou NV, Sampalis JS, Liberman M et al (2004) Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 240:416–423 (discussion 423–414)PubMedCrossRef
4.
go back to reference Perry CD, Hutter MM, Smith DB et al (2008) Survival and changes in comorbidities after bariatric surgery. Ann Surg 247:21–27PubMedCrossRef Perry CD, Hutter MM, Smith DB et al (2008) Survival and changes in comorbidities after bariatric surgery. Ann Surg 247:21–27PubMedCrossRef
5.
go back to reference Marceau P, Biron S, Bourque RA et al (1993) Biliopancreatic diversion with a new type of gastrectomy. Obes Surg 3:29–35PubMedCrossRef Marceau P, Biron S, Bourque RA et al (1993) Biliopancreatic diversion with a new type of gastrectomy. Obes Surg 3:29–35PubMedCrossRef
6.
go back to reference Cottam D, Qureshi FG, Mattar SG et al (2006) Laparoscopic sleeve gastrectomy as an initial weight-loss procedure for high-risk patients with morbid obesity. Surg Endosc 20:859–863PubMedCrossRef Cottam D, Qureshi FG, Mattar SG et al (2006) Laparoscopic sleeve gastrectomy as an initial weight-loss procedure for high-risk patients with morbid obesity. Surg Endosc 20:859–863PubMedCrossRef
7.
go back to reference Menenakos E, Stamou KM, Albanopoulos K et al (2010) Laparoscopic sleeve gastrectomy performed with intent to treat morbid obesity: a prospective single-center study of 261 patients with a median follow-up of 1 year. Obes Surg 20:276–282PubMedCrossRef Menenakos E, Stamou KM, Albanopoulos K et al (2010) Laparoscopic sleeve gastrectomy performed with intent to treat morbid obesity: a prospective single-center study of 261 patients with a median follow-up of 1 year. Obes Surg 20:276–282PubMedCrossRef
8.
go back to reference Uglioni B, Wolnerhanssen B, Peters T et al (2009) Midterm results of primary vs. secondary laparoscopic sleeve gastrectomy (LSG) as an isolated operation. Obes Surg 19:401–406PubMedCrossRef Uglioni B, Wolnerhanssen B, Peters T et al (2009) Midterm results of primary vs. secondary laparoscopic sleeve gastrectomy (LSG) as an isolated operation. Obes Surg 19:401–406PubMedCrossRef
9.
go back to reference Gagner M, Deitel M, Kalberer TL et al (2009) The Second International Consensus Summit for Sleeve Gastrectomy, March 19–21, 2009. Surg Obes Relat Dis 5:476–485PubMedCrossRef Gagner M, Deitel M, Kalberer TL et al (2009) The Second International Consensus Summit for Sleeve Gastrectomy, March 19–21, 2009. Surg Obes Relat Dis 5:476–485PubMedCrossRef
10.
go back to reference Akkary E, Duffy A, Bell R (2008) Deciphering the sleeve: technique, indications, efficacy, and safety of sleeve gastrectomy. Obes Surg 18:1323–1329PubMedCrossRef Akkary E, Duffy A, Bell R (2008) Deciphering the sleeve: technique, indications, efficacy, and safety of sleeve gastrectomy. Obes Surg 18:1323–1329PubMedCrossRef
11.
go back to reference Bohdjalian A, Langer FB, Shakeri-Leidenmuhler S et al (2010) Sleeve gastrectomy as sole and definitive bariatric procedure: 5-year results for weight loss and ghrelin. Obes Surg 20:535–540PubMedCrossRef Bohdjalian A, Langer FB, Shakeri-Leidenmuhler S et al (2010) Sleeve gastrectomy as sole and definitive bariatric procedure: 5-year results for weight loss and ghrelin. Obes Surg 20:535–540PubMedCrossRef
12.
go back to reference Langer FB, Reza Hoda MA, Bohdjalian A et al (2005) Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels. Obes Surg 15:1024–1029PubMedCrossRef Langer FB, Reza Hoda MA, Bohdjalian A et al (2005) Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels. Obes Surg 15:1024–1029PubMedCrossRef
13.
go back to reference Tschop M, Weyer C, Tataranni PA et al (2001) Circulating ghrelin levels are decreased in human obesity. Diabetes 50:707–709PubMedCrossRef Tschop M, Weyer C, Tataranni PA et al (2001) Circulating ghrelin levels are decreased in human obesity. Diabetes 50:707–709PubMedCrossRef
14.
go back to reference Ueno H, Yamaguchi H, Kangawa K et al (2005) Ghrelin: a gastric peptide that regulates food intake and energy homeostasis. Regul Pept 126:11–19PubMedCrossRef Ueno H, Yamaguchi H, Kangawa K et al (2005) Ghrelin: a gastric peptide that regulates food intake and energy homeostasis. Regul Pept 126:11–19PubMedCrossRef
15.
go back to reference Takiguchi S, Adachi S, Yamamoto K et al (2012) Mapping analysis of ghrelin producing cells in the human stomach associated with chronic gastritis and early cancers. Dig Dis Sci 57:1238–1246PubMedCrossRef Takiguchi S, Adachi S, Yamamoto K et al (2012) Mapping analysis of ghrelin producing cells in the human stomach associated with chronic gastritis and early cancers. Dig Dis Sci 57:1238–1246PubMedCrossRef
16.
go back to reference Regan JP, Inabnet WB, Gagner M et al (2003) Early experience with two-stage laparoscopic Roux-en-Y gastric bypass as an alternative in the super–super obese patient. Obes Surg 13:861–864PubMedCrossRef Regan JP, Inabnet WB, Gagner M et al (2003) Early experience with two-stage laparoscopic Roux-en-Y gastric bypass as an alternative in the super–super obese patient. Obes Surg 13:861–864PubMedCrossRef
17.
go back to reference Kasama K, Tagaya N, Kanehira E et al (2009) Laparoscopic sleeve gastrectomy with duodenojejunal bypass: technique and preliminary results. Obes Surg 19:1341–1345PubMedCrossRef Kasama K, Tagaya N, Kanehira E et al (2009) Laparoscopic sleeve gastrectomy with duodenojejunal bypass: technique and preliminary results. Obes Surg 19:1341–1345PubMedCrossRef
18.
go back to reference Akamizu T, Shinomiya T, Irako T et al (2005) Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy subjects using a new direct ELISA assay. J Clin Endocrinol Metab 90:6–9PubMedCrossRef Akamizu T, Shinomiya T, Irako T et al (2005) Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy subjects using a new direct ELISA assay. J Clin Endocrinol Metab 90:6–9PubMedCrossRef
19.
go back to reference Hosoda H, Kojima M, Matsuo H et al (2000) Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 279:909–913PubMedCrossRef Hosoda H, Kojima M, Matsuo H et al (2000) Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal tissue. Biochem Biophys Res Commun 279:909–913PubMedCrossRef
20.
go back to reference Nagaya N, Kojima M, Uematsu M et al (2001) Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol 280:R1483–R1487 Nagaya N, Kojima M, Uematsu M et al (2001) Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol 280:R1483–R1487
21.
go back to reference Kojima M, Hosoda H, Date Y et al (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660PubMedCrossRef Kojima M, Hosoda H, Date Y et al (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660PubMedCrossRef
22.
go back to reference Akamizu T, Kangawa K (2006) Translational research on the clinical applications of ghrelin. Endocr J 53:585–591PubMedCrossRef Akamizu T, Kangawa K (2006) Translational research on the clinical applications of ghrelin. Endocr J 53:585–591PubMedCrossRef
23.
go back to reference Fujitsuka N, Asakawa A, Amitani H et al (2012) Ghrelin and gastrointestinal movement. Methods Enzymol 514:289–301PubMedCrossRef Fujitsuka N, Asakawa A, Amitani H et al (2012) Ghrelin and gastrointestinal movement. Methods Enzymol 514:289–301PubMedCrossRef
24.
go back to reference Nagaya N, Uematsu M, Kojima M et al (2001) Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation 104:1430–1435PubMedCrossRef Nagaya N, Uematsu M, Kojima M et al (2001) Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation 104:1430–1435PubMedCrossRef
25.
go back to reference Miki K, Maekura R, Nagaya N et al (2012) Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled trial. PLoS One 7:e35708PubMedCrossRef Miki K, Maekura R, Nagaya N et al (2012) Ghrelin treatment of cachectic patients with chronic obstructive pulmonary disease: a multicenter, randomized, double-blind, placebo-controlled trial. PLoS One 7:e35708PubMedCrossRef
26.
go back to reference Li WG, Gavrila D, Liu X et al (2004) Ghrelin inhibits proinflammatory responses and nuclear factor-kappaβ activation in human endothelial cells. Circulation 109:2221–2226PubMedCrossRef Li WG, Gavrila D, Liu X et al (2004) Ghrelin inhibits proinflammatory responses and nuclear factor-kappaβ activation in human endothelial cells. Circulation 109:2221–2226PubMedCrossRef
27.
go back to reference Cummings DE, Weigle DS, Frayo RS et al (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346:1623–1630PubMedCrossRef Cummings DE, Weigle DS, Frayo RS et al (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346:1623–1630PubMedCrossRef
28.
go back to reference Goitein D, Lederfein D, Tzioni R et al (2012) Mapping of ghrelin gene expression and cell distribution in the stomach of morbidly obese patients: a possible guide for efficient sleeve gastrectomy construction. Obes Surg 22:617–622PubMedCrossRef Goitein D, Lederfein D, Tzioni R et al (2012) Mapping of ghrelin gene expression and cell distribution in the stomach of morbidly obese patients: a possible guide for efficient sleeve gastrectomy construction. Obes Surg 22:617–622PubMedCrossRef
29.
go back to reference Maksud FA, Alves JS, Diniz MT et al (2011) Density of ghrelin-producing cells is higher in the gastric mucosa of morbidly obese patients. Eur J Endocrinol 165:57–62PubMedCrossRef Maksud FA, Alves JS, Diniz MT et al (2011) Density of ghrelin-producing cells is higher in the gastric mucosa of morbidly obese patients. Eur J Endocrinol 165:57–62PubMedCrossRef
30.
go back to reference Akamizu T, Kangawa K (2011) Therapeutic applications of ghrelin to cachexia utilizing its appetite-stimulating effect. Peptides 32:2295–2300PubMedCrossRef Akamizu T, Kangawa K (2011) Therapeutic applications of ghrelin to cachexia utilizing its appetite-stimulating effect. Peptides 32:2295–2300PubMedCrossRef
31.
go back to reference Zub-Pokrowiecka A, Rembiasz K, Konturek SJ et al (2010) Ghrelin in diseases of the gastric mucosa associated with Helicobacter pylori infection. Med Sci Monit 16:CR493–CR500PubMed Zub-Pokrowiecka A, Rembiasz K, Konturek SJ et al (2010) Ghrelin in diseases of the gastric mucosa associated with Helicobacter pylori infection. Med Sci Monit 16:CR493–CR500PubMed
32.
go back to reference Natalucci G, Riedl S, Gleiss A et al (2005) Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern. Eur J Endocrinol 152:845–850PubMedCrossRef Natalucci G, Riedl S, Gleiss A et al (2005) Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern. Eur J Endocrinol 152:845–850PubMedCrossRef
33.
go back to reference Spiegel K, Tasali E, Leproult R et al (2011) Twenty-four-hour profiles of acylated and total ghrelin: relationship with glucose levels and impact of time of day and sleep. J Clin Endocrinol Metab 6:486–493CrossRef Spiegel K, Tasali E, Leproult R et al (2011) Twenty-four-hour profiles of acylated and total ghrelin: relationship with glucose levels and impact of time of day and sleep. J Clin Endocrinol Metab 6:486–493CrossRef
34.
go back to reference Goel N, Stunkard AJ, Rogers NL et al (2009) Circadian rhythm profiles in women with night eating syndrome. J Biol Rhythms 24:85–94PubMedCrossRef Goel N, Stunkard AJ, Rogers NL et al (2009) Circadian rhythm profiles in women with night eating syndrome. J Biol Rhythms 24:85–94PubMedCrossRef
35.
go back to reference Deitel M (2003) Overweight and obesity worldwide now estimated to involve 1.7 billion people. Obes Surg 13:329–330PubMedCrossRef Deitel M (2003) Overweight and obesity worldwide now estimated to involve 1.7 billion people. Obes Surg 13:329–330PubMedCrossRef
Metadata
Title
Clinical Significance of Ghrelin Expression in the Gastric Mucosa of Morbidly Obese Patients
Authors
Yasuhiro Miyazaki
Shuji Takiguchi
Yosuke Seki
Kazunori Kasama
Tsuyoshi Takahashi
Yukinori Kurokawa
Makoto Yamasaki
Hiroshi Miyata
Kiyokazu Nakajima
Masaki Mori
Yuichiro Doki
Publication date
01-12-2013
Publisher
Springer US
Published in
World Journal of Surgery / Issue 12/2013
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-013-2209-0

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