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Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections
  1. Pawan Noel1,
  2. Krutika Patel1,
  3. Chandra Durgampudi2,
  4. Ram N Trivedi1,
  5. Cristiane de Oliveira1,
  6. Michael D Crowell1,
  7. Rahul Pannala1,
  8. Kenneth Lee4,
  9. Randall Brand5,
  10. Jennifer Chennat5,
  11. Adam Slivka5,
  12. Georgios I Papachristou5,
  13. Asif Khalid5,
  14. David C Whitcomb5,
  15. James P DeLany5,
  16. Rachel A Cline5,
  17. Chathur Acharya2,
  18. Deepthi Jaligama2,
  19. Faris M Murad6,
  20. Dhiraj Yadav5,
  21. Sarah Navina3,
  22. Vijay P Singh1
  1. 1Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA
  2. 2Departments of Medicine, University of Pittsburgh Medical Center, Pasavant, Pennsylvania, USA
  3. 3Departments of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  4. 4Departments of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
  5. 5Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  6. 6Departments of Medicine, Washington University, Saint Louis, Missouri, USA
  1. Correspondence to Dr Vijay P Singh, Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ 85259, USA; singh.vijay{at}


Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators.

Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat.

Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat.

Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.


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