Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation
| Autor: | Kenneth K.W. Lee, Deepthi Jaligama, Dhiraj Yadav, Krutika Patel, Sarah Navina, Vijay P. Singh, Georgios I. Papachristou, Ram N. Trivedi, Chathur Acharya, Chandra Durgampudi, Pawan Noel, Faris Murad, Rachel Cline, James P. DeLany |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Lipolysis Systemic inflammation Severity of Illness Index Pathology and Forensic Medicine chemistry.chemical_compound Cetilistat Internal medicine medicine Animals Humans Enzyme Inhibitors Rats Wistar Triglyceride business.industry Pancreatitis Acute Necrotizing Regular Article Lipase medicine.disease Rats Endocrinology chemistry Lipotoxicity Lipase inhibitors Fatty Acids Unsaturated Pancreatitis Acute pancreatitis Female medicine.symptom business |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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