| Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity. | |
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MedLine Citation:
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PMID: 22049070 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Science translational medicine Volume: 3 ISSN: 1946-6242 ISO Abbreviation: Sci Transl Med Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-03 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101505086 Medline TA: Sci Transl Med Country: United States |
Other Details:
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Languages: eng Pagination: 107ra110 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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