title: Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity.
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: Department of Pathology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
authors: Sarah
authors: S
authors: Navina
authors: Chathur
authors: C
authors: Acharya
authors: James P
authors: JP
authors: DeLany
authors: Lidiya S
authors: LS
authors: Orlichenko
authors: Catherine J
authors: CJ
authors: Baty
authors: Sruti S
authors: SS
authors: Shiva
authors: Chandra
authors: C
authors: Durgampudi
authors: Jenny M
authors: JM
authors: Karlsson
authors: Kenneth
authors: K
authors: Lee
authors: Kyongtae T
authors: KT
authors: Bae
authors: Alessandro
authors: A
authors: Furlan
authors: Jaideep
authors: J
authors: Behari
authors: Shiguang
authors: S
authors: Liu
authors: Teresa
authors: T
authors: McHale
authors: Larry
authors: L
authors: Nichols
authors: Georgios Ioannis
authors: GI
authors: Papachristou
authors: Dhiraj
authors: D
authors: Yadav
authors: Vijay P
authors: VP
authors: Singh
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000473:pathology; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008066:Lipolysis / Q000502:physiology*; D051379:Mice; D008820:Mice, Obese; D009102:Multiple Organ Failure / Q000209:etiology* / Q000378:metabolism*; D009336:Necrosis / Q000209:etiology / Q000378:metabolism; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology*; D010195:Pancreatitis / Q000378:metabolism* / Q000503:physiopathology; D019283:Pancreatitis, Acute Necrotizing / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated