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, Dennis R.; Liu, Huilin; Miller, Matthew E.; Ramsden, Christopher E.; Gao, Bin; Feldstein, Ariel E.; Schuster, Susanne; McClain, Craig J. & Kirpich, Irina A.
  
• 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, Christopher E.; Hennebelle, Marie; Schuster, Susanne; Keyes, Gregory S.; Johnson, Casey D.; Kirpich, Irina A.; Dahlen, Jeff E.; Horowitz, Mark S.; Zamora, Daisy; Feldstein, Ariel E.; McClain, Craig J.; Muhlhausler, Beverly S.; Makrides, Maria; Gibson, Robert A. & Taha, Ameer Y.
  
• Oxidized linoleic acid metabolites induce liver mitochondrial dysfunction, apoptosis, and NLRP3 activation in mice. J Lipid Res. 2018 Sep;59(9):1597-1609
  Schuster, Susanne; Johnson, Casey D.; Hennebelle, Marie; Holtmann, Theresa; Taha, Ameer Y.; Kirpich, Irina A.; Eguchi, Akiko; Ramsden, Christopher E.; Papouchado, Bettina G.; McClain, Craig J. & Feldstein, Ariel E.