Carboxyl Ester Lipase May Not Mediate Lipotoxic Injury during Severe Acute Pancreatitis.

Acute lipolysis of visceral fat or circulating triglycerides may worsen acute pancreatitis-associated local and systemic injury. The pancreas expresses pancreatic triacylglycerol lipase (PNLIP), pancreatic lipase related protein 2 (PNLIPRP2), and carboxyl ester lipase (CEL), which may leak into the visceral fat or systemic circulation during pancreatitis. We thus aimed to determine the pancreatic lipase(s) regulating lipotoxicity during acute pancreatitis. For this acute pancreatitis-associated fat necrosis (FN) was analyzed using western blotting. Bile acid (liquid chromatography-tandem mass spectrometry/mass spectrometry) and fatty acid (using gas chromatography) concentrations were measured in human FN. The FN milieu was simulated in vitro using glyceryl trilinoleate, since linoleic acid is increased in FN. The bile acid requirements to effectively hydrolyze glyceryl trilinoleate were studied using exogenous or overexpressed lipases. The renal cell line (HEK 293) was used to study lipotoxic injury. Since dual pancreatic lipase knockouts are lethal, exocrine parotid acini lacking lipases were used to verify the results. PNLIP, PNLIPRP2, and CEL were increased in fat necrosis. Although PNLIP and PNLIPRP2 were equipotent in inducing lipolysis and lipotoxic injury, CEL required bile acid concentrations higher than in human fat necrosis. The high bile acid requirements for effective lipolysis make CEL an unlikely mediator of lipotoxic injury in acute pancreatitis. It remains to be explored whether PNLIP or PNLIPRP2 worsens acute pancreatitis severity in vivo.