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 (Lep db) 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 pfu), 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 six hours). The other half received saline on the same schedule. Serum APN concentration and pancreatic tissue levels of interleukin-6 (IL-6), interleukin-1 β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were measured by ELISA. Histologic pancreatitis score was determined by 2 experienced observers based on the degree of inflammation (0-4), edema (0-4) and vacuolization (0-4). Data were analyzed by ANOVA and Tukey tests; p<0.05 was considered significant.Results: No difference in body weight was observed among groups. Serum APN (mg/ml), pancreatic tissue concentration of IL-6, IL-1β and MCP-1(pg/ml), and pancreatitis score are shown in the Table.Conclusions: These data show that: 1) adenovirus administration significantly upregulates serum adiponectin concentration; 2) adiponectin upregulation significantly decreases pancreatic tissue IL-6 level, however, 3) does not change pancreatic IL-1β, MCP-1, or histologic pancreatitis severity. Adiponectin upregulation modulates the pancreatic cytokine milieu, but does not attenuate pancreatitis in this model of mild acute pancreatitis.

Group	Adiponectin	IL-6	IL-1β	MCP-1	Pancreatitis score
β gal-saline	5±1	6±1	10±1	16±2	0.3±0.0
APN-saline	60±5 §	6±1	15±4	23±4	0.3±0.0
β gal-caerulein	5±1	262±41*	267±46*	854±126*	7.9±0.7*
APN- Caerulein	78±10 §†	127±40*δ	202±27*	659±137*	7.4±0.9*

* p <0.001 vs. saline, §p <0.001 vs. β gal, δ p<0.02 vs. β gal-caerulein , † p< 0.05 vs. APN-saline