Document Detail


Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity.
MedLine Citation:
PMID:  22049070     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid-mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis.
Authors:
Sarah Navina; Chathur Acharya; James P DeLany; Lidiya S Orlichenko; Catherine J Baty; Sruti S Shiva; Chandra Durgampudi; Jenny M Karlsson; Kenneth Lee; Kyongtae T Bae; Alessandro Furlan; Jaideep Behari; Shiguang Liu; Teresa McHale; Larry Nichols; Georgios Ioannis Papachristou; Dhiraj Yadav; Vijay P Singh
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Science translational medicine     Volume:  3     ISSN:  1946-6242     ISO Abbreviation:  Sci Transl Med     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-03     Completed Date:  2012-05-17     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101505086     Medline TA:  Sci Transl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  107ra110     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
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MeSH Terms
Descriptor/Qualifier:
Acinar Cells / metabolism,  pathology
Animals
Fatty Acids / metabolism
Fatty Acids, Unsaturated / metabolism
Humans
Immunohistochemistry
Lipolysis / physiology*
Mice
Mice, Obese
Multiple Organ Failure / etiology*,  metabolism*
Necrosis / etiology,  metabolism
Obesity / metabolism*,  physiopathology
Pancreas / metabolism*,  pathology*
Pancreatitis / metabolism*,  physiopathology
Pancreatitis, Acute Necrotizing / metabolism,  pathology,  physiopathology
Grant Support
ID/Acronym/Agency:
R01 DK092460/DK/NIDDK NIH HHS; R01 DK092460-01/DK/NIDDK NIH HHS; R01DK092460/DK/NIDDK NIH HHS; UL1 RR024153/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Fatty Acids, Unsaturated
Comments/Corrections
Comment In:
Nat Rev Gastroenterol Hepatol. 2012 Jan;9(1):5   [PMID:  22143268 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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