Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity

Science Translational Medicine

Volumn 3, Issue 107, 2011, Pages

  Navina, Sarah ^a   Acharya, Chathur ^b   DeLany, James P ^a   Orlichenko, Lidiya S ^a   Baty, Catherine J ^a   Shiva, Sruti S ^a   Durgampudi, Chandra ^b   Karlsson, Jenny M ^a   Lee, Kenneth ^b   Bae, Kyongtae T ^a   Furlan, Alessandro ^a   Behari, Jaideep ^a   Liu, Shiguang ^a   McHale, Teresa ^a   Nichols, Larry ^a   Papachristou, Georgios Ioannis ^a   Yadav, Dhiraj ^a   Singh, Vijay P ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCIUM; CYTOCHROME C OXIDASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); RESISTIN; UNSATURATED FATTY ACID; FATTY ACID;

ACINAR CELL; ACUTE PANCREATITIS; ADIPOCYTE; ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CALCIUM CELL LEVEL; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE EXACERBATION; DISEASE SEVERITY; FATTY ACID BLOOD LEVEL; FEMALE; HUMAN; HUMAN TISSUE; HYPOCALCEMIA; IN VITRO STUDY; INFLAMMATION; KIDNEY DISEASE; LIPOLYSIS; LIPOTOXICITY; LUNG DISEASE; MALE; MORTALITY; MOUSE; MULTIPLE ORGAN FAILURE; NONHUMAN; OBESITY; PANCREAS NECROSIS; PRIORITY JOURNAL; ACUTE HEMORRHAGIC PANCREATITIS; ANIMAL; IMMUNOHISTOCHEMISTRY; METABOLISM; MOUSE MUTANT; NECROSIS; PANCREAS; PANCREATITIS; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY;

ACINAR CELLS; ANIMALS; FATTY ACIDS; FATTY ACIDS, UNSATURATED; HUMANS; IMMUNOHISTOCHEMISTRY; LIPOLYSIS; MICE; MICE, OBESE; MULTIPLE ORGAN FAILURE; NECROSIS; OBESITY; PANCREAS; PANCREATITIS; PANCREATITIS, ACUTE NECROTIZING;

EID: 80455129106     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3002573     Document Type: Article

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90. Acknowledgments: We thank M. Kienholz, R. Brand, M. Lowe, and D. Whitcomb for a critical appraisal of this manuscript. Funding: Supported by grant number UL1 RR024153 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research (S.N. and V.P.S.), and award number R01DK092460 (V.P.S.) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The contents of the manuscript are solely the responsibility of the authors and do not necessarily represent the official view of NCRR, NIDDK, or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/ overviewtranslational. asp. Also supported by a startup package from the University of Pittsburgh Department of Medicine (V.P.S.). Author contributions: S.N. designed the methodologies for, provided access to, and supervised the analysis of autopsy data and histological analysis, and provided funding for the project. C.A. analyzed and quantified intrapancreatic fat, necrosis, and peri-fat acinar necrosis. J.P.D. measured, analyzed, and interpreted the NEFA concentrations. L.S.O. conducted the experiments involving Western blotting. C.J.B. supervised the calcium studies and interpretation of the data. S.S.S. designed, conducted, and interpreted the mitochondrial complex activity assays. C.D. executed the animal model of pancreatitis. J.M.K. conducted and analyzed the calcium studies. K.L. identified SAP patients and provided the pancreatic necrosis debridement fluid. K.T.B. designed and supervised the analysis and interpretation of CT data. A.F. designed and conducted the measurements on CT data. J.B. helped in designing and supervised the analysis and interpretation of polymerase chain reaction (PCR) data. S.L. conducted and analyzed the PCR studies. T.M. conducted, analyzed, and interpreted electron microscopy data. L.N. helped design and interpret autopsy studies. G.I.P. provided data on CT scans and clinical severity of endoscopic retrograde cholangiopancreatography pancreatitis. D.Y. analyzed and interpreted clinical statistics. V.P.S. designed and supervised the overall execution of the project, conducted and interpreted experimental in vitro and in vivo studies, and provided funding for the project. Competing interests: The authors declare that they have no competing interests.