Free Fatty Acid Aggravate Severe Acute Pancreatitis In Obese Mice Through NLRP3-caspase1 Signal Pathway In Macrophages

Objective and aims: Overweight is an important cause and risk factor of severe acute pancreatitis(SAP).However,the deeper mechanism that obesity influence severe acute pancreatitis has not been fully elucidated.The purpose of our research is to figure out the relation between macrophages NLRP3-caspase1 inflammasome pathway and free fatty acid(FFA)in obesity relared severe acute pancreatitis.Methods: Male C57BL/6 mice were randomly assigned into six groups.Half of all mice were fed with high fat diet to induce obese mice model.The rest of the mice were fed with normal diet to induce normal mice model.SAP mice model were induced by administration of cerulein and lipopolysaccharide.After 2 hours of lipopolysaccharide injected,half of SAP model mice were administered orlistat by intraperitoneal injections.The rest of SAP model mice were administered same dose normal saline by intraperitoneal injections.Pancreatic inflammation was measured by pancreatic histology change and serum biochemical changes.Pancreatic macrophages infiltration and NLRP3-caspase1 inflammasome passway activation were measured by western blot,immunofluorescence and immunohistochemistry.Results:(1)In mice with obese severe acute pancreatitis,pathologic modification of pancreatic inflammation was increased,and serum levels of TG,FFA,and MCP-1 were up-regulated.(2)Pancreatic macrophages infiltration was rised in obesity related severe acute pancreatitis.Macrophages NLRP3-caspase1 inflammasomes passway was obviously activated in obesity related severe acute pancreatitis.(3)In obese SAP treated by orlistat,pancreatic inflammation got releaved.Orlistat resulted in a decrease in level of serum TG,FFA,and MCP-1 in obesity related SAP treated with orlistat compared with obese mice with SAP.(4)Pancreatic macrophages infiltration was decreased in obesity related acute pancreatitis treated by orlistat compared with obesity related acute pancreatitis.NLRP3-caspase1 inflammasomes passway in macrophages was down-regulated in obesity related severe acute pancreatitis treated by orlistat compared with obese mice with SAP.Conclusion: Increased free fatty acid promote macrophages infiltration and NLRP3-caspase1 passway activation which may result in the intensification of obesity related acute pancreatitis.