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Article: Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity

TitleLipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity
Authors
Issue Date2011
Citation
Science Translational Medicine, 2011, v. 3, n. 107, article no. 107ra110 How to Cite?
AbstractObesity 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.
Persistent Identifierhttp://hdl.handle.net/10722/316056
ISSN
2023 Impact Factor: 15.8
2023 SCImago Journal Rankings: 6.510
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNavina, Sarah-
dc.contributor.authorAcharya, Chathur-
dc.contributor.authorDeLany, James P.-
dc.contributor.authorOrlichenko, Lidiya S.-
dc.contributor.authorBaty, Catherine J.-
dc.contributor.authorShiva, Sruti S.-
dc.contributor.authorDurgampudi, Chandra-
dc.contributor.authorKarlsson, Jenny M.-
dc.contributor.authorLee, Kenneth-
dc.contributor.authorBae, Kyongtae T.-
dc.contributor.authorFurlan, Alessandro-
dc.contributor.authorBehari, Jaideep-
dc.contributor.authorLiu, Shiguang-
dc.contributor.authorMcHale, Teresa-
dc.contributor.authorNichols, Larry-
dc.contributor.authorPapachristou, Georgios Ioannis-
dc.contributor.authorYadav, Dhiraj-
dc.contributor.authorSingh, Vijay P.-
dc.date.accessioned2022-08-24T15:49:05Z-
dc.date.available2022-08-24T15:49:05Z-
dc.date.issued2011-
dc.identifier.citationScience Translational Medicine, 2011, v. 3, n. 107, article no. 107ra110-
dc.identifier.issn1946-6234-
dc.identifier.urihttp://hdl.handle.net/10722/316056-
dc.description.abstractObesity 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.-
dc.languageeng-
dc.relation.ispartofScience Translational Medicine-
dc.titleLipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1126/scitranslmed.3002573-
dc.identifier.pmid22049070-
dc.identifier.scopuseid_2-s2.0-80455129106-
dc.identifier.volume3-
dc.identifier.issue107-
dc.identifier.spagearticle no. 107ra110-
dc.identifier.epagearticle no. 107ra110-
dc.identifier.eissn1946-6242-
dc.identifier.isiWOS:000296750400004-
dc.identifier.f100013394966-

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