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

Gut. 2008 Oct;57(10):1431-40. doi: 10.1136/gut.2007.135665. Epub 2008 Jun 25.

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 microg/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 alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adiponectin / metabolism
  • Adiponectin / physiology*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Ceruletide
  • Dietary Fats / administration & dosage
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / complications
  • Pancreatitis / chemically induced
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Pancreatitis / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Adiponectin
  • Dietary Fats
  • Ceruletide