Obese rats exhibit high levels of fat necrosis and isoprostanes in taurocholate-induced acute pancreatitis

Obesity is a prognostic factor for severity in acute pancreatitis in humans. Our aim was to assess the role of oxidative stress and abdominal fat in the increased severity of acute pancreatitis in obese rats. Taurocholate-induced acute pancreatitis was performed in lean and obese Zucker rats. Levels...

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Veröffentlicht in:PloS one 2012-09, Vol.7 (9), p.e44383
Hauptverfasser: Pereda, Javier, Pérez, Salvador, Escobar, Javier, Arduini, Alessandro, Asensi, Miguel, Serviddio, Gaetano, Sabater, Luis, Aparisi, Luis, Sastre, Juan
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container_issue 9
container_start_page e44383
container_title PloS one
container_volume 7
creator Pereda, Javier
Pérez, Salvador
Escobar, Javier
Arduini, Alessandro
Asensi, Miguel
Serviddio, Gaetano
Sabater, Luis
Aparisi, Luis
Sastre, Juan
description Obesity is a prognostic factor for severity in acute pancreatitis in humans. Our aim was to assess the role of oxidative stress and abdominal fat in the increased severity of acute pancreatitis in obese rats. Taurocholate-induced acute pancreatitis was performed in lean and obese Zucker rats. Levels of reduced glutathione, oxidized glutathione, L-cysteine, cystine, and S-adenosylmethionine were measured in pancreas as well as the activities of serine/threonine protein phosphatases PP1 and PP2A and tyrosin phosphatases. Isoprostane, malondialdehyde, triglyceride, and free fatty acid levels and lipase activity were measured in plasma and ascites. Lipase activity was measured in white adipose tissue with and without necrosis and confirmed by western blotting. Under basal conditions obese rats exhibited lower reduced glutathione levels in pancreas and higher triglyceride and free fatty acid levels in plasma than lean rats. S-adenosyl methionine levels were markedly increased in pancreas of obese rats. Acute pancreatitis in obese rats led to glutathione oxidation and lower reduced glutathione levels in pancreas together with decreased activities of redox-sensitive phosphatases PP1, and PP2A. S-adenosyl methionine levels decreased but cystine levels increased markedly in pancreas upon pancreatitis. Acute pancreatitis triggered an increase in isoprostane levels in plasma and ascites in obese rats. Free fatty acid levels were extremely high in pancreatitis-associated ascitic fluid from obese rats and lipase was bound with great affinity to white adipose tissue, especially to areas of necrosis. Our results show that oxidative stress occurs locally and systemically in obese rats with pancreatitis favouring inactivation of protein phosphatases in pancreas, which would promote up-regulation of pro-inflammatory cytokines, and the increase of isoprostanes which might cause powerful pulmonary and renal vasoconstriction. Future studies are needed to confirm the translational relevance of the present findings obtained in a rat model of taurocholate-induced pancreatic damage and necrosis.
doi_str_mv 10.1371/journal.pone.0044383
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Our aim was to assess the role of oxidative stress and abdominal fat in the increased severity of acute pancreatitis in obese rats. Taurocholate-induced acute pancreatitis was performed in lean and obese Zucker rats. Levels of reduced glutathione, oxidized glutathione, L-cysteine, cystine, and S-adenosylmethionine were measured in pancreas as well as the activities of serine/threonine protein phosphatases PP1 and PP2A and tyrosin phosphatases. Isoprostane, malondialdehyde, triglyceride, and free fatty acid levels and lipase activity were measured in plasma and ascites. Lipase activity was measured in white adipose tissue with and without necrosis and confirmed by western blotting. Under basal conditions obese rats exhibited lower reduced glutathione levels in pancreas and higher triglyceride and free fatty acid levels in plasma than lean rats. S-adenosyl methionine levels were markedly increased in pancreas of obese rats. 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Kay</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Obese rats exhibit high levels of fat necrosis and isoprostanes in taurocholate-induced acute pancreatitis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-09-18</date><risdate>2012</risdate><volume>7</volume><issue>9</issue><spage>e44383</spage><pages>e44383-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Obesity is a prognostic factor for severity in acute pancreatitis in humans. Our aim was to assess the role of oxidative stress and abdominal fat in the increased severity of acute pancreatitis in obese rats. Taurocholate-induced acute pancreatitis was performed in lean and obese Zucker rats. Levels of reduced glutathione, oxidized glutathione, L-cysteine, cystine, and S-adenosylmethionine were measured in pancreas as well as the activities of serine/threonine protein phosphatases PP1 and PP2A and tyrosin phosphatases. Isoprostane, malondialdehyde, triglyceride, and free fatty acid levels and lipase activity were measured in plasma and ascites. Lipase activity was measured in white adipose tissue with and without necrosis and confirmed by western blotting. Under basal conditions obese rats exhibited lower reduced glutathione levels in pancreas and higher triglyceride and free fatty acid levels in plasma than lean rats. S-adenosyl methionine levels were markedly increased in pancreas of obese rats. Acute pancreatitis in obese rats led to glutathione oxidation and lower reduced glutathione levels in pancreas together with decreased activities of redox-sensitive phosphatases PP1, and PP2A. S-adenosyl methionine levels decreased but cystine levels increased markedly in pancreas upon pancreatitis. Acute pancreatitis triggered an increase in isoprostane levels in plasma and ascites in obese rats. Free fatty acid levels were extremely high in pancreatitis-associated ascitic fluid from obese rats and lipase was bound with great affinity to white adipose tissue, especially to areas of necrosis. Our results show that oxidative stress occurs locally and systemically in obese rats with pancreatitis favouring inactivation of protein phosphatases in pancreas, which would promote up-regulation of pro-inflammatory cytokines, and the increase of isoprostanes which might cause powerful pulmonary and renal vasoconstriction. Future studies are needed to confirm the translational relevance of the present findings obtained in a rat model of taurocholate-induced pancreatic damage and necrosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23028532</pmid><doi>10.1371/journal.pone.0044383</doi><tpages>e44383</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2012-09, Vol.7 (9), p.e44383
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1344508742
source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry
subjects Adenosylmethionine
Adipose tissue
Animals
Ascites
Ascitic fluid
Biology
Blotting, Western
Causes of
Cell cycle
Chemical compounds
Complications and side effects
Cystine
Cytokines
Deactivation
Development and progression
Fatty acids
Genetic aspects
Glutathione
Glutathione - metabolism
Inactivation
Inflammation
Isoprostanes
Isoprostanes - metabolism
Kidneys
Laboratory animals
Lipase
Lipid peroxidation
Lipids
Male
Malondialdehyde
Malondialdehyde - metabolism
Medicine
Methionine
Necrosis
Obesity
Obesity - metabolism
Obesity - physiopathology
Oxidation
Oxidative Stress
Pancreas
Pancreas - enzymology
Pancreas - metabolism
Pancreas - pathology
Pancreatitis
Pancreatitis, Acute Necrotizing - chemically induced
Pancreatitis, Acute Necrotizing - metabolism
Pancreatitis, Acute Necrotizing - pathology
Pharmacy
Physiology
Rats
Rats, Zucker
Rodents
S-Adenosylmethionine
Serine
Taurocholic Acid - toxicity
Threonine
Triglycerides - metabolism
Tumor necrosis factor-TNF
Vasoconstriction
Western blotting
title Obese rats exhibit high levels of fat necrosis and isoprostanes in taurocholate-induced acute pancreatitis
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