title: A high-fat diet temporarily renders Sod1-deficient mice resistant to an oxidative insult.
abstract: Patients with nonalcoholic fatty liver disease may subsequently develop nonalcoholic steatohepatitis after suffering from a second insult, such as oxidative stress. Aim of this study was to investigate the pathogenesis of the liver injury caused when lipids accumulate under conditions of intrinsic oxidative stress using mice that are deficient in superoxide dismutase 1 (SOD1) and the leptin receptor (Lepr). We established Sod1-/-::Leprdb/dbmice and carried out analyses of four groups of genetically modified mice, namely, wild type, Sod1-/-, Leprdb/dband Sod1-/-::Leprdb/dbmice. Mice with defects in the SOD1 or Lepr gene are vulnerable to developing fatty livers, even when fed a normal diet. Feeding a high-fat diet (HFD) caused an increase in the number of lipid droplets in the liver to different extents in each genotypic mouse. an HFD caused the accelerated death of db/db mice, but contradictory to our expectations, the death rates for the Sod1-deficient mice were decreased by feeding HFD. Consistent with the improved probability of survival, liver damage was significantly ameliorated by feeding an HFD compared to a normal diet in the mice with an Sod1-deficient background. Oxidative stress markers, hyperoxidized peroxiredoxin and lipid peroxidation products, were decreased somewhat in Sod1-/-mice by feeding HFD. We conclude that lipids reacted with reactive oxygen species and eliminated them in the livers of the young mice, which resulted in the alleviation of oxidative stress, but in advanced age oxidized products accumulated, leading to the aggravation of the liver injury and an increase in fatality rate.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Junitsu
authors.initials: J
authors.lastname: Ito
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Akihara
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Jaeyong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Takujiro
authors.initials: T
authors.lastname: Homma
authors.affiliation: Department of Public Health, Yamagata University Graduate School of Medical Science, 2-2-2 Iidanishi, Yamagata 990-9585, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kawasaki
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan. Electronic address: jfujii@med.id.yamagata-u.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D015227:Lipid Peroxidation; D008099:Liver / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000503:physiopathology*; D018384:Oxidative Stress; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D054411:Receptors, Leptin; D014280:Triglycerides; C515447:leptin receptor, mouse; C000606291:Sod1 protein, mouse; D000072105:Superoxide Dismutase-1
keywords: High-fat diet; Lipophagy; Liver steatosis; Oxidative stress; Superoxide dismutase