Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

Pawan Noel, Krutika Patel, Chandra Durgampudi, Ram N. Trivedi, Cristiane De Oliveira, Michael D. Crowell, Rahul Pannala, Kenneth Lee, Randall Brand, Jennifer Chennat, Adam Slivka, Georgios I. Papachristou, Asif Khalid, David C. Whitcomb, James P. DeLany, Rachel A. Cline, Chathur Acharya, Deepthi Jaligama, Faris M. Murad, Dhiraj YadavSarah Navina, Vijay Prem Singh

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalGut
DOIs
StateAccepted/In press - Dec 10 2014

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Fat Necrosis
Unsaturated Fatty Acids
Pancreatitis
Necrosis
Interleukin-1
Triolein
Ceruletide
Lipolysis
Interleukin-8
Blood Cells
Fats
Oleic Acids
Cytokines
Linoleic Acids
Chemotactic Factors
Lipase
Pancreatic Neoplasms
Keratinocytes
Oncogenes
Pneumonia

ASJC Scopus subject areas

  • Gastroenterology

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Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections. / Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N.; De Oliveira, Cristiane; Crowell, Michael D.; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I.; Khalid, Asif; Whitcomb, David C.; DeLany, James P.; Cline, Rachel A.; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M.; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay Prem.

In: Gut, 10.12.2014.

Research output: Contribution to journalArticle

Noel, P, Patel, K, Durgampudi, C, Trivedi, RN, De Oliveira, C, Crowell, MD, Pannala, R, Lee, K, Brand, R, Chennat, J, Slivka, A, Papachristou, GI, Khalid, A, Whitcomb, DC, DeLany, JP, Cline, RA, Acharya, C, Jaligama, D, Murad, FM, Yadav, D, Navina, S & Singh, VP 2014, 'Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections', Gut. https://doi.org/10.1136/gutjnl-2014-308043
Noel, Pawan ; Patel, Krutika ; Durgampudi, Chandra ; Trivedi, Ram N. ; De Oliveira, Cristiane ; Crowell, Michael D. ; Pannala, Rahul ; Lee, Kenneth ; Brand, Randall ; Chennat, Jennifer ; Slivka, Adam ; Papachristou, Georgios I. ; Khalid, Asif ; Whitcomb, David C. ; DeLany, James P. ; Cline, Rachel A. ; Acharya, Chathur ; Jaligama, Deepthi ; Murad, Faris M. ; Yadav, Dhiraj ; Navina, Sarah ; Singh, Vijay Prem. / Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections. In: Gut. 2014.
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abstract = "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.",
author = "Pawan Noel and Krutika Patel and Chandra Durgampudi and Trivedi, {Ram N.} and {De Oliveira}, Cristiane and Crowell, {Michael D.} and Rahul Pannala and Kenneth Lee and Randall Brand and Jennifer Chennat and Adam Slivka and Papachristou, {Georgios I.} and Asif Khalid and Whitcomb, {David C.} and DeLany, {James P.} and Cline, {Rachel A.} and Chathur Acharya and Deepthi Jaligama and Murad, {Faris M.} and Dhiraj Yadav and Sarah Navina and Singh, {Vijay Prem}",
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T1 - Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

AU - Noel, Pawan

AU - Patel, Krutika

AU - Durgampudi, Chandra

AU - Trivedi, Ram N.

AU - De Oliveira, Cristiane

AU - Crowell, Michael D.

AU - Pannala, Rahul

AU - Lee, Kenneth

AU - Brand, Randall

AU - Chennat, Jennifer

AU - Slivka, Adam

AU - Papachristou, Georgios I.

AU - Khalid, Asif

AU - Whitcomb, David C.

AU - DeLany, James P.

AU - Cline, Rachel A.

AU - Acharya, Chathur

AU - Jaligama, Deepthi

AU - Murad, Faris M.

AU - Yadav, Dhiraj

AU - Navina, Sarah

AU - Singh, Vijay Prem

PY - 2014/12/10

Y1 - 2014/12/10

N2 - 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.

AB - 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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