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

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

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)1226-1240
Number of pages15
JournalAmerican Journal of Pathology
Volume189
Issue number6
DOIs
StatePublished - Jun 1 2019

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Lipase
Pancreatitis
Esters
Fat Necrosis
Wounds and Injuries
Bile Acids and Salts
Lipolysis
Intra-Abdominal Fat
HEK293 Cells
Linoleic Acid
Gas Chromatography
Pancreas
Mass Spectrometry
Triglycerides
Fatty Acids
Western Blotting
Kidney

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Carboxyl Ester Lipase May Not Mediate Lipotoxic Injury during Severe Acute Pancreatitis. / Khatua, Biswajit; Trivedi, Ram N.; Noel, Pawan; Patel, Krutika; Singh, Ravinder Jit; de Oliveira, Cristiane; Trivedi, Shubham; Mishra, Vivek; Lowe, Mark; Singh, Vijay Prem.

In: American Journal of Pathology, Vol. 189, No. 6, 01.06.2019, p. 1226-1240.

Research output: Contribution to journalArticle

Khatua, B, Trivedi, RN, Noel, P, Patel, K, Singh, RJ, de Oliveira, C, Trivedi, S, Mishra, V, Lowe, M & Singh, VP 2019, 'Carboxyl Ester Lipase May Not Mediate Lipotoxic Injury during Severe Acute Pancreatitis', American Journal of Pathology, vol. 189, no. 6, pp. 1226-1240. https://doi.org/10.1016/j.ajpath.2019.02.015
Khatua, Biswajit ; Trivedi, Ram N. ; Noel, Pawan ; Patel, Krutika ; Singh, Ravinder Jit ; de Oliveira, Cristiane ; Trivedi, Shubham ; Mishra, Vivek ; Lowe, Mark ; Singh, Vijay Prem. / Carboxyl Ester Lipase May Not Mediate Lipotoxic Injury during Severe Acute Pancreatitis. In: American Journal of Pathology. 2019 ; Vol. 189, No. 6. pp. 1226-1240.
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