title: High-salt in addition to high-fat diet may enhance inflammation and fibrosis in liver steatosis induced by oxidative stress and dyslipidemia in mice.
abstract: BACKGROUND
  It is widely known that salt is an accelerating factor for the progression of metabolic syndrome and causes cardiovascular diseases, most likely due to its pro-oxidant properties. We hypothesized that excessive salt intake also facilitates the development of nonalcoholic steatohepatitis (NASH), which is frequently associated with metabolic syndrome.
  
  
  METHODS
  We examined the exacerbating effect of high-salt diet on high-fat diet-induced liver injury in a susceptible model to oxidative stress, apoE knockout and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transgenic mice.
  
  
  RESULTS
  High-salt diet led to NASH in high-fat diet-fed LOX-1 transgenic/apoE knockout mice without affecting high-fat diet-induced dyslipidemia or hepatic triglyceride accumulation. Additionally, a high-salt and high-fat diet stimulated oxidative stress production and inflammatory reaction to a greater extent than did a high-fat diet in the liver of LOX-1 transgenic/apoE knockout mice.
  
  
  CONCLUSIONS
  We demonstrated that high-salt diet exacerbated NASH in high-fat diet-fed LOX-1 transgenic /apoE knockout mice and that this effect was associated with the stimulation of oxidative and inflammatory processes; this is the first study to suggest the important role of excessive salt intake in the development of NASH.
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. yuetake-tky@umin.ac.jp.|Office for Research Ethics Support, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. yuetake-tky@umin.ac.jp.
authors.forename: Yuzaburo
authors.initials: Y
authors.lastname: Uetake
authors.affiliation: Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan. ikeda-1im@h.u-tokyo.ac.jp.|Department of Gastroenterology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. ikeda-1im@h.u-tokyo.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Department of Pathology, Kawasaki Municipal Hospital, Kawasaki, Japan. ries@royal.ocn.ne.jp.
authors.forename: Rie
authors.initials: R
authors.lastname: Irie
authors.affiliation: Department of Gastroenterology, Toshiba General Hospital, Tokyo, Japan. kazuaki.tejima@toshiba.co.jp.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Tejima
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. hmatsui-tky@umin.ac.jp.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. sayokoogura@hotmail.com.|Division of Laboratory Medicine, Department of Pathology and Microbiology, Faculty of Medicine, Nihon University School of Medicine, Tokyo, Japan. sayokoogura@hotmail.com.
authors.forename: Sayoko
authors.initials: S
authors.lastname: Ogura
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. wanghong224@gmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. mushengyu218@yahoo.co.jp.
authors.forename: ShengYu
authors.initials: S
authors.lastname: Mu
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. daigoro-daigoro@hotmail.co.jp.
authors.forename: Daigoro
authors.initials: D
authors.lastname: Hirohama
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. katsua-tky@umin.ac.jp.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ando
authors.affiliation: Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan. t-sawamura@umin.ac.jp.|Department of Physiology, Shinshu University School of Medicine, Nagano, Japan. t-sawamura@umin.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.affiliation: Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan. yatomiy-lab@h.u-tokyo.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. Toshiro.FUJITA@rcast.u-tokyo.ac.jp.|Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan. Toshiro.FUJITA@rcast.u-tokyo.ac.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan. tshimo-tky@umin.ac.jp.|Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan. tshimo-tky@umin.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shimosawa
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects*; D050171:Dyslipidemias / Q000150:complications* / Q000473:pathology; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology; D005355:Fibrosis / Q000209:etiology; D007249:Inflammation / Q000209:etiology; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis / Q000235:genetics; D012982:Sodium, Dietary / Q000009:adverse effects*; D013481:Superoxides / Q000032:analysis
chemical_list: C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; D012982:Sodium, Dietary; D013481:Superoxides; D009249:NADP