Acute lipotoxicity regulates severity of biliary acute pancreatitis without affecting its initiation

Chandra Durgampudi, Pawan Noel, Krutika Patel, Rachel Cline, Ram N. Trivedi, James P. Delany, Dhiraj Yadav, Georgios I. Papachristou, Kenneth Lee, Chathur Acharya, Deepthi Jaligama, Sarah Navina, Faris Murad, Vijay Prem Singh

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O-positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate-induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction.

Original languageEnglish (US)
Pages (from-to)1773-1784
Number of pages12
JournalAmerican Journal of Pathology
Volume184
Issue number6
DOIs
StatePublished - 2014

    Fingerprint

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Durgampudi, C., Noel, P., Patel, K., Cline, R., Trivedi, R. N., Delany, J. P., Yadav, D., Papachristou, G. I., Lee, K., Acharya, C., Jaligama, D., Navina, S., Murad, F., & Singh, V. P. (2014). Acute lipotoxicity regulates severity of biliary acute pancreatitis without affecting its initiation. American Journal of Pathology, 184(6), 1773-1784. https://doi.org/10.1016/j.ajpath.2014.02.015