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Gut 57:1431-1440 doi:10.1136/gut.2007.135665
  • Pancreas

Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet

  1. H Araki1,2,
  2. T Nishihara1,2,
  3. M Matsuda2,
  4. A Fukuhara2,
  5. S Kihara2,
  6. T Funahashi2,
  7. T R Kataoka3,
  8. Y Kamada1,
  9. T Kiyohara1,
  10. S Tamura1,
  11. N Hayashi1,
  12. I Shimomura2
  1. 1
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka, Japan
  2. 2
    Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
  3. 3
    Department of Stem Cell Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan
  1. Dr T Nishihara, Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, K1, 2–2 Yamadaoka, Suita, Osaka 565–0871, Japan; tamaon{at}gh.med.osaka-u.ac.jp
  • Revised 21 April 2008
  • Accepted 27 May 2008
  • Published Online First 25 June 2008

Abstract

Background: Obesity is a risk factor for acute pancreatitis (AP), but the molecular mechanism remains unclear. Adiponectin, an adipose tissue-derived secretory factor, has anti-inflammatory properties in addition to various biological functions, and its plasma concentrations are reduced in obese subjects. However, the role of adiponectin in AP has not been investigated.

Aim: To determine the effects of adiponectin on AP.

Methods: We investigated the effects of adiponectin on experimental AP by using adiponectin-knockout (APN-KO) mice and adenovirus-mediated adiponectin over-expression. AP was induced by 10 hourly intraperitoneal injections of low-dose caerulein (10 μg/kg) after 2 week feeding of normal chow or a high-fat diet (HFD) in wild-type (WT) and APN-KO mice. We evaluated the severity of AP biochemically and morphologically.

Results: Low-dose caerulein treatment did not induce pancreatic damage in either WT or APN-KO mice under normal chow feeding. APN-KO mice, but not WT mice, fed a HFD and then treated with caerulein developed pancreatic damage and inflammation, accompanied by increased macrophage/neutrophil infiltration and upregulation of pro-inflammatory mediators such as tumour necrosis factor α in the pancreas. Adenovirus-mediated over-expression of adiponectin attenuated the severity of HFD/caerulein-induced AP in APN-KO mice.

Conclusions: Adiponectin plays a protective role in caerulein-induced AP in HFD-fed mice.

Footnotes

  • ▸ A supplementary figure is published online only at http://gut.bmj.com/content/vol57/issue10

  • Funding: This study was supported by a grant from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.

  • Competing interests: None.

  • Ethics approval: Approval for this study was granted by the Committee for Animal Experimentation of Osaka University on 14 March 2006.