Cannabinoid receptor-1 blockade attenuates acute pancreatitis in obesity by an adiponectin mediated mechanism.
J Gastrointest Surg
; 13(5): 831-8, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19225848
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 (Lep(Db)) 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 microg/g hourly x 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-alpha (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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Pancreatite
/
Piperidinas
/
Pirazóis
/
Receptor CB1 de Canabinoide
/
Obesidade
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Gastrointest Surg
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos