Cannabinoid Receptor-1 Blockade Attenuates Acute pancreatitis in Obesity by An adiponectin Mediated Mechanism

  • Nicholas J. Zyromski
  • Abhishek Mathur
  • Henry A. Pitt
  • Terence E. Wade
  • Sue Wang
  • Deborah A. Swartz-Basile
  • Andrew D. Prather
  • Keith D. Lillemoe
2008 SSAT Poster Presentation Manuscript

Abstract

Background

Obesity is a risk factor for increased severity of acute pancreatitis. Adipocytes produce adiponectin, an anti-inflammatory molecule that is paradoxically decreased in the setting of obesity. We have shown that adiponectin concentration inversely mirrors the severity of pancreatitis in obese mice. Cannabinoid receptor CB-1 blockade increases circulating adiponectin concentration. We, therefore, hypothesize that blockade of CB-1 would increase adiponectin and attenuate pancreatitis severity.

Methods

Forty lean (C57BL/6J) and 40 obese (LepDb) mice were studied. Half of the mice in each strain received intraperitoneal injection of the CB-1 antagonist rimonabant (10 mg/kg daily for 7 days); the others received vehicle. Pancreatitis was induced by intraperitoneal injection of cerulein (50 μg/g hourly ×6). Pancreatitis severity was determined by histology. Pancreatic chemokine and proinflammatory cytokine concentrations were measured by ELISA.

Results

Rimonabant treatment significantly increased circulating adiponectin concentration in obese mice (p < 0.03 vs. vehicle). After induction of pancreatitis, obese mice treated with rimonabant had significantly decreased histologic pancreatitis (p < 0.001), significantly lower pancreatic tissue levels of monocyte chemoattractant protein-1 (p = 0.03), tumor necrosis factor-α (p < 0.001), interleukin-6 (p < 0.001), and myeloperoxidase (p = 0.006) relative to vehicle-treated animals.

Conclusions

In obese mice, cannabinoid receptor CB-1 blockade with rimonabant attenuates the severity of acute pancreatitis by an adiponectin-mediated mechanism.

Keywords

Pancreatitis Cannabinoid Adiponectin Obesity 

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Copyright information

© The Society for Surgery of the Alimentary Tract 2009

Authors and Affiliations

  • Nicholas J. Zyromski
    • 1
  • Abhishek Mathur
    • 1
  • Henry A. Pitt
    • 1
  • Terence E. Wade
    • 1
  • Sue Wang
    • 1
  • Deborah A. Swartz-Basile
    • 1
  • Andrew D. Prather
    • 1
  • Keith D. Lillemoe
    • 1
  1. 1.Department of SurgeryIndiana University School of MedicineIndianapolisUSA

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