Journal of Gastroenterology

, Volume 46, Issue 12, pp 1361–1367 | Cite as

Association of low serum adiponectin levels with erosive esophagitis in men: an analysis of 2405 subjects undergoing physical check-ups

  • Motohiko Kato
  • Kenji WatabeEmail author
  • Toshimitsu Hamasaki
  • Miyuki Umeda
  • Aiko Furubayashi
  • Kazuo Kinoshita
  • Osamu Kishida
  • Takashi Fujimoto
  • Akira Yamada
  • Yoshifumi Tsukamoto
  • Shunsuke Yamamoto
  • Yoshihiro Kamada
  • Yuichi Yoshida
  • Shinichi Kiso
  • Shusaku Tsutsui
  • Shinji Kihara
  • Norio Hayashi
  • Yuji Matsuzawa
Original Article—Alimentary Tract



Obesity is a risk factor for gastro-esophageal reflux disease (GERD). It is generally considered that intra-abdominal pressure in obese subjects is involved in the pathogenesis of GERD through acid exposure to the esophagus. Recently, visceral fat has been recognized as an endocrine organ that secretes various adipocytokines including adiponectin. The aim of this study was to elucidate the relation between adiponectin and erosive esophagitis.


This was a cross-sectional retrospective observational study: 2405 consecutive subjects who underwent screening esophago-gastro-duodenoscopy with serum adiponectin measurement as part of their physical check-up programs were analyzed. Clinical factors were compared between subjects with and without erosive esophagitis. The association between adiponectin and erosive esophagitis was assessed using a bootstrapping re-sampling method after adjustment for factors that tended to be different in univariate analysis.


Serum adiponectin levels were significantly lower in those with erosive esophagitis (8.17 μg/ml) than in those without (10.1). The erosive esophagitis group had a greater body mass index (BMI) and waist circumference (WC) and a higher prevalence of hiatal hernia. Using the bootstrap method, with a lower adiponectin cut-off value of 3–7 μg/ml, the lower limit of the 95% confidence interval of the adjusted odds ratio consistently exceeded 1 after adjustment for BMI and hiatal hernia in men. When adjusting for WC instead of BMI, the effect of adiponectin was reduced but remained significant at a lower cut-off value (3–3.5 μg/ml).


Low serum adiponectin levels may be associated with an increased risk for erosive esophagitis in men.


Esophagitis Adiponectin Obesity 



The authors thank Shoji Ishitani at Sumitomo Hospital for assiduous effort in collecting the data from the annual physical check-up records. This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    El-Serag HB, Petersen NJ, Carter J, Graham DY, Richardson P, Genta RM, et al. Gastroesophageal reflux among different racial groups in the United States. Gastroenterology. 2004;126:1692–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997;112:1448–56.PubMedCrossRefGoogle Scholar
  3. 3.
    Fujiwara Y, Arakawa T. Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol. 2009;44:518–34.PubMedCrossRefGoogle Scholar
  4. 4.
    El-Serag H. The association between obesity and GERD: a review of the epidemiological evidence. Dig Dis Sci. 2008;53:2307–12.PubMedCrossRefGoogle Scholar
  5. 5.
    Corley DA, Kubo A. Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis. Am J Gastroenterol. 2006;101:2619–28.PubMedCrossRefGoogle Scholar
  6. 6.
    Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143:199–211.PubMedGoogle Scholar
  7. 7.
    Kang MS, Park DI, Oh SY, Yoo TW, Ryu SH, Park JH, et al. Abdominal obesity is an independent risk factor for erosive esophagitis in a Korean population. J Gastroenterol Hepatol. 2007;22:1656–61.PubMedCrossRefGoogle Scholar
  8. 8.
    Lee HL, Eun CS, Lee OY, Jeon YC, Han DS, Yoon BC, et al. Association between erosive esophagitis and visceral fat accumulation quantified by abdominal CT scan. J Clin Gastroenterol. 2009;43:240–3.PubMedCrossRefGoogle Scholar
  9. 9.
    Nam SY, Choi IJ, Ryu KH, Park BJ, Kim HB, Nam BH. Abdominal visceral adipose tissue volume is associated with increased risk of erosive esophagitis in men and women. Gastroenterology. 2010;139:1902–11.PubMedCrossRefGoogle Scholar
  10. 10.
    Matsuzawa Y. Adiponectin: a key player in obesity related disorders. Curr Pharm Des. 2010;16:1896–901.PubMedCrossRefGoogle Scholar
  11. 11.
    Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun. 1996;221:286–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257:79–83.PubMedCrossRefGoogle Scholar
  13. 13.
    Kamada Y, Matsumoto H, Tamura S, Fukushima J, Kiso S, Fukui K, et al. Hypoadiponectinemia accelerates hepatic tumor formation in a nonalcoholic steatohepatitis mouse model. J Hepatol. 2007;47:556–64.PubMedCrossRefGoogle Scholar
  14. 14.
    Nishihara T, Matsuda M, Araki H, Oshima K, Kihara S, Funahashi T, et al. Effect of adiponectin on murine colitis induced by dextran sulfate sodium. Gastroenterology. 2006;131:853–61.PubMedCrossRefGoogle Scholar
  15. 15.
    Araki H, Nishihara T, Matsuda M, Fukuhara A, Kihara S, Funahashi T, et al. Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet. Gut. 2008;57:1431–40.PubMedCrossRefGoogle Scholar
  16. 16.
    Yamada T, Araki H, Watabe K, Kamada Y, Kiso S, Ogiyama H, et al. Adiponectin deficiency enhanced the severity of cerulein-induced chronic pancreatitis in mice. J Gastroenterol. 2010;45(7):742–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J. Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology. 2004;40:46–54.PubMedCrossRefGoogle Scholar
  18. 18.
    Yamamoto K, Kiyohara T, Murayama Y, Kihara S, Okamoto Y, Funahashi T, et al. Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn’s disease. Gut. 2005;54:789–96.PubMedCrossRefGoogle Scholar
  19. 19.
    Sharma A, Muddana V, Lamb J, Greer J, Papachristou GI, Whitcomb DC. Low serum adiponectin levels are associated with systemic organ failure in acute pancreatitis. Pancreas. 2009;38:907–12.PubMedCrossRefGoogle Scholar
  20. 20.
    Efron B, Tibshirani R. An introduction to the bootstrap. Boca Raton: Chapman & Hall/CRC Press; 1993.Google Scholar
  21. 21.
    Wu JC, Mui LM, Cheung CM, Chan Y, Sung JJ. Obesity is associated with increased transient lower esophageal sphincter relaxation. Gastroenterology. 2007;132:883–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Dent J, Holloway RH, Toouli J, Dodds WJ. Mechanisms of lower oesophageal sphincter incompetence in patients with symptomatic gastrooesophageal reflux. Gut. 1988;29:1020–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Kahrilas PJ, Shi G, Manka M, Joehl RJ. Increased frequency of transient lower esophageal sphincter relaxation induced by gastric distention in reflux patients with hiatal hernia. Gastroenterology. 2000;118:688–95.PubMedCrossRefGoogle Scholar
  24. 24.
    Matsumoto H, Tamura S, Kamada Y, Kiso S, Fukushima J, Wada A, et al. Adiponectin deficiency exacerbates lipopolysaccharide/d-galactosamine-induced liver injury in mice. World J Gastroenterol. 2006;12:3352–8.PubMedGoogle Scholar
  25. 25.
    Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000;96:1723–32.PubMedGoogle Scholar
  26. 26.
    Ohashi K, Parker JL, Ouchi N, Higuchi A, Vita JA, Gokce N, et al. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem. 2010;285:6153–60.PubMedCrossRefGoogle Scholar
  27. 27.
    Sennello JA, Fayad R, Morris AM, Eckel RH, Asilmaz E, Montez J, et al. Regulation of T cell-mediated hepatic inflammation by adiponectin and leptin. Endocrinology. 2005;146:2157–64.PubMedCrossRefGoogle Scholar
  28. 28.
    Allende DS, Yerian LM. Diagnosing gastroesophageal reflux disease: the pathologist’s perspective. Adv Anat Pathol. 2009;16:161–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Souza RF, Huo X, Mittal V, Schuler CM, Carmack SW, Zhang HY, et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology. 2009;137:1776–84.PubMedCrossRefGoogle Scholar
  30. 30.
    Hamaguchi M, Fujiwara Y, Takashima T, Hayakawa T, Sasaki E, Shiba M, et al. Increased expression of cytokines and adhesion molecules in rat chronic esophagitis. Digestion. 2003;68:189–97.PubMedCrossRefGoogle Scholar
  31. 31.
    Adeniyi KO, Olowookorun MO. Influence of sex on gastric acid secretion and parietal cell mass in the rat. Acta Physiol Hung. 1989;74:63–7.PubMedGoogle Scholar
  32. 32.
    Straus EW, Raufman JP. Meal-stimulated gastrin release in normal men and women. J Assoc Acad Minor Phys. 1989;1:9–10.PubMedGoogle Scholar
  33. 33.
    Machowska A, Szlachcic A, Pawlik M, Brzozowski T, Konturek SJ, Pawlik WW. The role of female and male sex hormones in the healing process of preexisting lingual and gastric ulcerations. J Physiol Pharmacol. 2004;55(Suppl 2):91–104.PubMedGoogle Scholar
  34. 34.
    Liu ES, Wong BC, Cho CH. Influence of gender difference and gastritis on gastric ulcer formation in rats. J Gastroenterol Hepatol. 2001;16:740–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes. 2002;51:2734–41.PubMedCrossRefGoogle Scholar
  36. 36.
    Corley DA, Kubo A, Levin TR, Block G, Habel L, Zhao W, et al. Abdominal obesity and body mass index as risk factors for Barrett’s esophagus. Gastroenterology. 2007;133:34–41.PubMedCrossRefGoogle Scholar
  37. 37.
    Edelstein ZR, Farrow DC, Bronner MP, Rosen SN, Vaughan TL. Central adiposity and risk of Barrett’s esophagus. Gastroenterology. 2007;133:403–11.PubMedCrossRefGoogle Scholar
  38. 38.
    Rubenstein JH, Kao JY, Madanick RD, Zhang M, Wang M, Spacek MB, et al. Association of adiponectin multimers with Barrett’s oesophagus. Gut. 2009;58:1583–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Schober F, Neumeier M, Weigert J, Wurm S, Wanninger J, Schäffler A, et al. Low molecular weight adiponectin negatively correlates with the waist circumference and monocytic IL-6 release. Biochem Biophys Res Commun. 2007;361:968–73.PubMedCrossRefGoogle Scholar
  40. 40.
    Lee YC, Yen AM, Tai JJ, Chang SH, Lin JT, Chiu HM, et al. The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease. Gut. 2009;58:174–81.PubMedCrossRefGoogle Scholar
  41. 41.
    Zagari RM, Fuccio L, Wallander MA, Johansson S, Fiocca R, Casanova S, et al. Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Loiano-Monghidoro study. Gut. 2008;57:1354–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  • Motohiko Kato
    • 1
  • Kenji Watabe
    • 1
    Email author
  • Toshimitsu Hamasaki
    • 2
  • Miyuki Umeda
    • 3
  • Aiko Furubayashi
    • 3
  • Kazuo Kinoshita
    • 3
  • Osamu Kishida
    • 3
  • Takashi Fujimoto
    • 3
  • Akira Yamada
    • 3
  • Yoshifumi Tsukamoto
    • 3
  • Shunsuke Yamamoto
    • 1
  • Yoshihiro Kamada
    • 1
  • Yuichi Yoshida
    • 1
  • Shinichi Kiso
    • 1
  • Shusaku Tsutsui
    • 1
  • Shinji Kihara
    • 4
  • Norio Hayashi
    • 5
  • Yuji Matsuzawa
    • 3
  1. 1.Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuitaJapan
  2. 2.Department of Biomedical StatisticsOsaka University Graduate School of MedicineSuitaJapan
  3. 3.Sumitomo HospitalOsakaJapan
  4. 4.Department of Biomedical InformaticsOsaka University Graduate School of MedicineSuitaJapan
  5. 5.Kansai Rosai HospitalAmagasakiJapan

Personalised recommendations