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

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)831-838
Number of pages8
JournalJournal of Gastrointestinal Surgery
Volume13
Issue number5
DOIs
StatePublished - May 1 2009

Keywords

  • Adiponectin
  • Cannabinoid
  • Obesity
  • Pancreatitis

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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    Zyromski, N. J., Mathur, A., Pitt, H. A., Wade, T. E., Wang, S., Swartz-Basile, D. A., Prather, A. D., & Lillemoe, K. D. (2009). Cannabinoid receptor-1 blockade attenuates acute pancreatitis in obesity by an adiponectin mediated mechanism. Journal of Gastrointestinal Surgery, 13(5), 831-838. https://doi.org/10.1007/s11605-009-0824-8