Biomaterial Database

Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections. 2016

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

Departments of Medicine, Mayo Clinic, Scottsdale, Arizona, USA.

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.

UI	MeSH Term	Description	Entries
D007963	Leukocytes, Mononuclear	Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.	Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D008066	Lipolysis	The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues.	Lipolyses
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009102	Multiple Organ Failure	A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative.	MODS,Multiple Organ Dysfunction Syndrome,Organ Dysfunction Syndrome, Multiple,Organ Failure, Multiple,Failure, Multiple Organ,Multiple Organ Failures
D010179	Pancreas	A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D010192	Pancreatic Pseudocyst	Cyst-like space not lined by EPITHELIUM and contained within the PANCREAS. Pancreatic pseudocysts account for most of the cystic collections in the pancreas and are often associated with chronic PANCREATITIS.	Pancreatic Pseudocysts,Pseudocyst, Pancreatic,Pseudocysts, Pancreatic
D005218	Fat Necrosis	A condition in which the death of adipose tissue results in neutral fats being split into fatty acids and glycerol.	Steatonecrosis,Fat Necroses,Necrosis, Fat,Steatonecroses
D005231	Fatty Acids, Unsaturated	FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.	Fatty Acids, Polyunsaturated,Polyunsaturated Fatty Acid,Unsaturated Fatty Acid,Polyunsaturated Fatty Acids,Acid, Polyunsaturated Fatty,Acid, Unsaturated Fatty,Acids, Polyunsaturated Fatty,Acids, Unsaturated Fatty,Fatty Acid, Polyunsaturated,Fatty Acid, Unsaturated,Unsaturated Fatty Acids
D005260	Female		Females