title: Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections.
abstract: OBJECTIVE
  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.
authors.affiliation: Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Pawan
authors.initials: P
authors.lastname: Noel
authors.affiliation: Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Krutika
authors.initials: K
authors.lastname: Patel
authors.affiliation: Departments of Medicine, University of Pittsburgh Medical Center, Pasavant, Pennsylvania, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Durgampudi
authors.affiliation: Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Ram N
authors.initials: RN
authors.lastname: Trivedi
authors.affiliation: Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Cristiane
authors.initials: C
authors.lastname: de Oliveira
authors.affiliation: Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Crowell
authors.affiliation: Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Pannala
authors.affiliation: Departments of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lee
authors.affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Brand
authors.affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chennat
authors.affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Slivka
authors.affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Georgios I
authors.initials: GI
authors.lastname: Papachristou
authors.affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Asif
authors.initials: A
authors.lastname: Khalid
authors.affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Whitcomb
authors.affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: DeLany
authors.affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Cline
authors.affiliation: Departments of Medicine, University of Pittsburgh Medical Center, Pasavant, Pennsylvania, USA.
authors.forename: Chathur
authors.initials: C
authors.lastname: Acharya
authors.affiliation: Departments of Medicine, University of Pittsburgh Medical Center, Pasavant, Pennsylvania, USA.
authors.forename: Deepthi
authors.initials: D
authors.lastname: Jaligama
authors.affiliation: Departments of Medicine, Washington University, Saint Louis, Missouri, USA.
authors.forename: Faris M
authors.initials: FM
authors.lastname: Murad
authors.affiliation: Departments of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Yadav
authors.affiliation: Departments of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Navina
authors.affiliation: Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.
authors.forename: Vijay P
authors.initials: VP
authors.lastname: Singh
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D005218:Fat Necrosis / Q000209:etiology / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology; D010179:Pancreas / Q000187:drug effects; D010192:Pancreatic Pseudocyst / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005231:Fatty Acids, Unsaturated; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D016209:Interleukin-8
keywords: OBESITY; PANCREATITIS