Oxidized Linoleic Acid metabolites (OXLAMs) play a critical role in the development and progression of alcohol-mediated hepatic injury

• Applicant: Dr. Susanne Gaul
• Subject Area: Gastroenterology
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 299295825

• Final Report Year: 2019

Final Report Abstract

In summary, the results of the current study support the concept that dietary LA, a ω-6-PUFA, exacerbates ethanol-induced liver injury and provides evidence that the increase in OXLAM production and promotion of an OXLAM-mediated pro-inflammatory response might be one of the underlying mechanisms. Strategies to decrease LA consumption through dietary modifications may be an effective approach to reduce ethanol-induced OXLAMs and to attenuate ALD.

Publications

• Dietary Linoleic Acid and Its Oxidized Metabolites Exacerbate Liver Injury Caused by Ethanol via Induction of Hepatic Proinflammatory Response in Mice. Am J Pathol. 2017 Oct;187(10):2232-2245
  Warner DR, Liu H, Miller ME, Ramsden CE, Gao B, Feldstein AE, Schuster S, McClain CJ, Kirpich IA
  (See online at https://doi.org/10.1016/j.ajpath.2017.06.008)
• Effects of diets enriched in linoleic acid and its peroxidation products on brain fatty acids, oxylipins, and aldehydes in mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Oct;1863(10):1206-1213
  Ramsden CE, Hennebelle M, Schuster S, Keyes GS, Johnson CD, Kirpich IA, Dahlen JE, Horowitz MS, Zamora D, Feldstein AE, McClain CJ, Muhlhausler BS, Makrides M, Gibson RA, Taha AY
  (See online at https://doi.org/10.1016/j.bbalip.2018.07.007)
• Oxidized linoleic acid metabolites induce liver mitochondrial dysfunction, apoptosis, and NLRP3 activation in mice. J Lipid Res. 2018 Sep;59(9):1597-1609
  Schuster S, Johnson CD, Hennebelle M, Holtmann T, Taha AY, Kirpich IA, Eguchi A, Ramsden CE, Papouchado BG, McClain CJ, Feldstein AE
  (See online at https://doi.org/10.1194/jlr.M083741)