Global Deletion of Glutathione S-Transferase A4 Exacerbates Developmental Nonalcoholic Steatohepatitis

We established a mouse model of developmental nonalcoholic steatohepatitis (NASH) by feeding a high polyunsaturated fat liquid diet to female glutathione-S-transferase 4-4 ( Gsta4−/− )/peroxisome proliferator activated receptor α ( Ppara−/− ) double knockout 129/SvJ mice for 12 weeks from weaning. W...

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Veröffentlicht in:	The American journal of pathology 2017-02, Vol.187 (2), p.418-430
Hauptverfasser:	Ronis, Martin, Mercer, Kelly, Engi, Bridgette, Pulliam, Casey, Zimniak, Piotr, Hennings, Leah, Shearn, Colin, Badger, Thomas, Petersen, Dennis
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Blotting, Western Diet, High-Fat Disease Models, Animal Female Glutathione Transferase - deficiency Lipid Peroxidation - physiology Liver - pathology Mice Mice, Knockout Non-alcoholic Fatty Liver Disease - enzymology Non-alcoholic Fatty Liver Disease - pathology Pathology Polymerase Chain Reaction PPAR alpha - deficiency Regular Transcriptome
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Zusammenfassung:	We established a mouse model of developmental nonalcoholic steatohepatitis (NASH) by feeding a high polyunsaturated fat liquid diet to female glutathione-S-transferase 4-4 ( Gsta4−/− )/peroxisome proliferator activated receptor α ( Ppara−/− ) double knockout 129/SvJ mice for 12 weeks from weaning. We used it to probe the importance of lipid peroxidation in progression of NASH beyond simple steatosis. Feeding Gsta4−/− / Ppara−/− double-knockout ( dKO ) mice liquid diets containing corn oil resulted in a percentage fat–dependent increase in steatosis and necroinflammatory injury ( P
ISSN:	0002-9440 1525-2191
DOI:	10.1016/j.ajpath.2016.10.022