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

Biswajit Khatua, Ram N. Trivedi, Pawan Noel, Krutika Patel, Ravinder Singh, Cristiane de Oliveira, Shubham Trivedi, Vivek Mishra, Mark Lowe, Vijay P. Singh

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2 Scopus citations

Abstract

Acute lipolysis of visceral fat or circulating triglycerides may worsen acute pancreatitis (AP)–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 AP. For this AP, associated fat necrosis was analyzed using Western blot analysis. Bile acid (using liquid chromatography–tandem mass spectrometry) and fatty acid (using gas chromatography) concentrations were measured in human fat necrosis. The fat necrosis milieu was simulated in vitro using glyceryl trilinoleate because linoleic acid is increased in fat necrosis. 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. Because 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 AP. It remains to be explored whether PNLIP or PNLIPRP2 worsens AP severity in vivo.

Original languageEnglish
Pages (from-to)1226-1240
Number of pages15
JournalAmerican Journal of Pathology
Volume189
Issue number6
DOIs
StatePublished - Jun 2019

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    Khatua, B., Trivedi, R. N., Noel, P., Patel, K., Singh, R., de Oliveira, C., Trivedi, S., Mishra, V., Lowe, M., & Singh, V. P. (2019). Carboxyl Ester Lipase May Not Mediate Lipotoxic Injury during Severe Acute Pancreatitis. American Journal of Pathology, 189(6), 1226-1240. https://doi.org/10.1016/j.ajpath.2019.02.015