Translational research : the journal of laboratory and clinical medicine
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Acute pancreatitis (AP), although most often a mild and self-limiting inflammatory disease, worsens to a characteristically necrotic severe acute pancreatitis (SAP) in about 20% of cases. Obesity, affecting more than one-third of American adults, is a risk factor for the development of SAP, but the exact mechanism of this association has not been identified. Coincidental with chronic low-grade inflammation, activation of the nucleotide-binding domain, leucine-rich containing family, pyrin-domain containing 3 (NLRP3) inflammasome increases with obesity. ⋯ Treatment with glyburide led to significantly reduced relative pancreatic mass and water content and less pancreatic damage and cell death in genetically obese ob/ob mice with SAP compared with vehicle-treated obese SAP mice. Glyburide administration in ob/ob mice with cerulein-induced SAP also resulted in significantly reduced serum levels of interleukin 6, lipase, and amylase and led to lower production of lipopolysaccharide-stimulated interleukin 1β release in cultured peritoneal cells, compared with vehicle-treated ob/ob mice with SAP. Together, these data indicate involvement of the NLRP3 inflammasome in obesity-associated SAP and expose the possible utility of its inhibition in prevention or treatment of SAP in obese individuals.