title: An SOD1 deficiency enhances lipid droplet accumulation in the fasted mouse liver by aborting lipophagy.
abstract: Under normal feeding conditions, oxidative stress stimulates lipid droplets accumulation in hepatocytes. We found that, despite the low visceral fat in Sod1-knockout (KO) mouse, lipid droplets accumulate in the liver to a greater extent than for the wild-type mouse upon fasting. Liver damage became evident in the KO mice. While fasting caused substantial endoplasmic reticulum stress in KO mice, the expression of genes involved in fatty acid production was suppressed. LC3-II, which is essential for the dynamic process of autophagosome formation, was activated in the wild-type mouse and enhanced in the KO mouse. However, the p62, an adapter protein with the ubiquitin- and LC3-binding activity, accumulated abnormally in the livers of KO mice, implying an abortive lipophagic process as the cause for the impaired lipid metabolism and the hepatic damage that occurs upon fasting.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 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, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Hamashima
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Shirato
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 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, Japan.
authors.forename: Takujiro
authors.initials: T
authors.lastname: Homma
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Japan.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Japan. Electronic address: jfujii@med.id.yamagata-u.ac.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
mesh_terms: D000818:Animals; D019923:Capsulorhexis; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005215:Fasting; D050356:Lipid Metabolism; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D000072105:Superoxide Dismutase-1
chemical_list: C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Fasting; Lipophagy; Liver steatosis; Oxidative stress; Superoxide dismutase