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Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity.
Sci Transl Med. 2011 Nov 02; 3(107):107ra110.ST

Abstract

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+Show Affiliations

Department of Pathology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22049070

Citation

Navina, Sarah, et al. "Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity." Science Translational Medicine, vol. 3, no. 107, 2011, pp. 107ra110.
Navina S, Acharya C, DeLany JP, et al. Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity. Sci Transl Med. 2011;3(107):107ra110.
Navina, S., Acharya, C., DeLany, J. P., Orlichenko, L. S., Baty, C. J., Shiva, S. S., Durgampudi, C., Karlsson, J. M., Lee, K., Bae, K. T., Furlan, A., Behari, J., Liu, S., McHale, T., Nichols, L., Papachristou, G. I., Yadav, D., & Singh, V. P. (2011). Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity. Science Translational Medicine, 3(107), 107ra110. https://doi.org/10.1126/scitranslmed.3002573
Navina S, et al. Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity. Sci Transl Med. 2011 Nov 2;3(107):107ra110. PubMed PMID: 22049070.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity. AU - Navina,Sarah, AU - Acharya,Chathur, AU - DeLany,James P, AU - Orlichenko,Lidiya S, AU - Baty,Catherine J, AU - Shiva,Sruti S, AU - Durgampudi,Chandra, AU - Karlsson,Jenny M, AU - Lee,Kenneth, AU - Bae,Kyongtae T, AU - Furlan,Alessandro, AU - Behari,Jaideep, AU - Liu,Shiguang, AU - McHale,Teresa, AU - Nichols,Larry, AU - Papachristou,Georgios Ioannis, AU - Yadav,Dhiraj, AU - Singh,Vijay P, PY - 2011/11/4/entrez PY - 2011/11/4/pubmed PY - 2012/5/18/medline SP - 107ra110 EP - 107ra110 JF - Science translational medicine JO - Sci Transl Med VL - 3 IS - 107 N2 - 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. SN - 1946-6242 UR - https://www.unboundmedicine.com/medline/citation/22049070/Lipotoxicity_causes_multisystem_organ_failure_and_exacerbates_acute_pancreatitis_in_obesity_ L2 - https:///www.science.org/doi/10.1126/scitranslmed.3002573?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -