Does Adiponectin Upregulation Attenuate the Severity of Acute Pancreatitis in Obesity?

Introduction: Obesity is an independent risk factor for severe acute pancreatitis, though the mechanisms underlying this association are unknown. The powerful anti-inflammatory adipokine adiponectin is decreased in obesity. We recently showed that the severity of pancreatitis in obese mice is inversely related to circulating adiponectin levels, and therefore hypothesized that adiponectin upregulation would attenuate the severity of pancreatitis in obese mice. Methods: Forty congenitally obese mice were studied. Seven days prior to study, 20 mice received a single tail vein injection of adenovirus expressing recombinant murine adiponectin (APN; 2 × 10 ⁸ plaque forming unit (pfu)), and the remainder received a control adenoviral vector expressing β-galactosidase (β-gal; 2 × 10 ⁸ pfu). Half of the mice in each group had pancreatitis induced by cerulein injection (50mcg/kg IP hourly for 6 h). The other half received saline on the same schedule. Serum APN concentration and pancreatic tissue concentrations of interleukin (IL)-6, IL-1β, and MCP-1 were measured by ELISA. Histologic pancreatitis score was calculated based on the degree of inflammation (0-4), edema (0-4), and vacuolization (0-4). Data were analyzed by ANOVA and Tukey's tests; p<0.05 was considered significant. Results: No difference in body weight was observed between groups. Serum APN was significantly upregulated in the APN group compared with the β-gal group. Pancreatic tissue concentration of IL-6 was significantly decreased in the APN group compared with the β-gal group. No change either in pancreatic tissue concentration of IL-1β and MCP-1 or in the severity of histologic pancreatitis were observed. Conclusion: Adiponectin upregulation modulates the pancreatic cytokine milieu but does not attenuate pancreatitis in this model of mild acute pancreatitis.