Adiponectin plays a protective role in caerulein-induced acute pancreatitis in mice fed a high-fat diet
- H Araki1,2,
- T Nishihara1,2,
- M Matsuda2,
- A Fukuhara2,
- S Kihara2,
- T Funahashi2,
- T R Kataoka3,
- Y Kamada1,
- T Kiyohara1,
- S Tamura1,
- N Hayashi1,
- I Shimomura2
- 1Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka, Japan
- 2Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan
- 3Department of Stem Cell Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan
- Dr T Nishihara, Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, K1, 2–2 Yamadaoka, Suita, Osaka 565–0871, Japan;
- Revised 21 April 2008
- Accepted 27 May 2008
- Published Online First 25 June 2008
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.
▸ 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.