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

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

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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
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume295
Issue number3
DOIs
StatePublished - Sep 2008

Fingerprint

Adipokines
Pancreatitis
Obesity
Ceruletide
Obese Mice
Adiponectin
Leptin
Neutrophil Activation
Wild Animals
Intraperitoneal Injections
Interleukin-1
Chemokines
Adipocytes
Adipose Tissue
Interleukin-6
Histology
Cytokines

Keywords

  • Adiponectin
  • Leptin

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis. / Zyromski, Nicholas; Mathur, Abhishek; Pitt, Henry A.; Lu, Debao; Gripe, John T.; Walker, Julia J.; Yancey, Kyle; Wade, Terence E.; Swartz-Basile, Deborah A.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 295, No. 3, 09.2008.

Research output: Contribution to journalArticle

Zyromski, Nicholas ; Mathur, Abhishek ; Pitt, Henry A. ; Lu, Debao ; Gripe, John T. ; Walker, Julia J. ; Yancey, Kyle ; Wade, Terence E. ; Swartz-Basile, Deborah A. / A murine model of obesity implicates the adipokine milieu in the pathogenesis of severe acute pancreatitis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2008 ; Vol. 295, No. 3.
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