A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis

Nicholas J. Zyromski, Abhishek Mathur, Henry A. Pitt, Debao Lu, John T. Gripe, Julia J. Walker, Kyle Yancey, Terence E. Wade, Deborah A. Swartz-Basile

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Obesity is clearly an independent risk factor for increased severity of acute pancreatitis (AP), although the mechanisms underlying this association are unknown. Adipokines (including leptin and adiponectin) are pleiotropic molecules produced by adipocytes that are important regulators of the inflammatory response. We hypothesized that the altered adipokine milieu observed in obesity contributes to the increased severity of pancreatitis. Lean (C57BL/6J), obese leptin-deficient (LepOb), and obese hyperleptinemic (LepDb) mice were subjected to AP by six hourly intraperitoneal injections of cerulein (50 μg/kg). Severity of AP was assessed by histology and by measuring pancreatic concentration of the proinflammatory cytokines IL-1β and IL-6, the chemokine MCP-1, and the marker of neutrophil activation MPO. Both congenitally obese strains of mice developed significantly more severe AP than wild-type lean animals. Severity of AP was not solely related to adipose tissue volume: LepOb mice were heaviest; however, LepDb mice developed the most severe AP both histologically and biochemically. Circulating adiponectin concentrations inversely mirrored the severity of pancreatitis. These data demonstrate that congenitally obese mice develop more severe AP than lean animals when challenged by cerulein hyperstimulation and suggest that alteration of the adipokine milieu exacerbates the severity of AP in obesity.

Original languageEnglish (US)
Pages (from-to)G552-G558
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume295
Issue number3
DOIs
StatePublished - Sep 1 2008

Keywords

  • Adiponectin
  • Leptin

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

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