WNIN Mutant Obese Rats Develop Acute Pancreatitis With the Enhanced Inflammatory Milieu

Abstract

Background: WNIN/Gr-Ob rats demonstrate features of metabolic syndrome that include obesity, insulin resistance, impaired glucose tolerance, and hyperinsulinemia. The impetus obtained from earlier studies on these rats demonstrates an inflammatory milieu peaking between 6 and 9 months of age in adipose, pancreas, and bone marrow/mesenchymal stem cells. Methods:We evaluated the outcome of L-arginine-induced acute pancreatitis, in WNIN/Gr-Ob rats as compared to control rats. We assessed key parameters associated with severity of acute pancreatitis such as pancreatic inflammation and extra-pancretic damage. Result:We demonstrated increased pancreatic inflammation (inflammatory cytokines, malondialdehyde, and reactive oxygen species) in WNIN/Gr-Ob rats as compared to the control rats administered with L-arginine. Increased systemic inflammation and islet dysfunction were also observed in WNIN/Gr-Ob rats as compared to control when L-arginine was administered. Molecular, cellular and biochemical data from our study indicate increased severity of pancreatitis in mutant rats as compared to control rats. Conclusion:We advocate WNIN/Gr-Ob rats as a novel model system to study the pathophysiology of severe acute pancreatitis associated with obesity.