title: Overexpression of Peroxiredoxin 4 Affects Intestinal Function in a Dietary Mouse Model of Nonalcoholic Fatty Liver Disease.
abstract: BACKGROUND
  Accumulating evidence has shown that methionine- and choline-deficient high fat (MCD+HF) diet induces the development of nonalcoholic fatty liver disease (NAFLD), in which elevated reactive oxygen species play a crucial role. We have reported that peroxiredoxin 4 (PRDX4), a unique secretory member of the PRDX antioxidant family, protects against NAFLD progression. However, the detailed mechanism and potential effects on the intestinal function still remain unclear.
  
  
  RESULTS
  Two weeks after feeding mice a MCD+HF diet, the livers of human PRDX4 transgenic (Tg) mice exhibited significant suppression in the development of NAFLD compared with wild-type (WT) mice. The serum thiobarbituric acid reactive substances levels were significantly lower in Tg mice. In contrast, the Tg small intestine with PRDX4 overexpression showed more suppressed shortening of total length and villi height, and more accumulation of lipid in the jejunum, along with lower levels of dihydroethidium binding. The enterocytes exhibited fewer apoptotic but more proliferating cells, and inflammation was reduced in the mucosa. Furthermore, the small intestine of Tg mice had significantly higher expression of cholesterol absorption-regulatory factors, including liver X receptor-α, but lower expression of microsomal triglyceride-transfer protein.
  
  
  CONCLUSIONS
  Our present data provide the first evidence of the beneficial effects of PRDX4 on intestinal function in the reduction of the severity of NAFLD, by ameliorating oxidative stress-induced local and systemic injury. We can suggest that both liver and intestine are spared, to some degree, by the antioxidant properties of PRDX4.
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.|The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Nawata
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Noguchi
authors.affiliation: Department of Cellular Pharmacology, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mazaki
authors.affiliation: Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University, Yamagata, 990-9585, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kurahashi
authors.affiliation: Department of Occupational Pneumology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.|Shared-Use Research Center, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Wang
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.|Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei, Medical University, Jiankang Road 12, Shijiazhuang, 050011, Hebei, China.|Department of Thoracic Surgery, Saitama Cancer Center, Saitama, 362-0806, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Uramoto
authors.affiliation: The President Laboratory, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.|Asahi-Matsumoto Hospital, Kitakyushu, 800-0242, Japan.
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
authors.affiliation: Department of Microbiology, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Hatsumi
authors.initials: H
authors.lastname: Taniguchi
authors.affiliation: The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University, Yamagata, 990-9585, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.|Laboratory of Pathology, Fukuoka Wajiro Hospital, Fukuoka, 811-0213, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
authors.affiliation: Department of Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.|Department of Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan.|Institute of Pathology, Medical University of Graz, Graz, 8010, Austria.|Institute of Molecular Biosciences, University of Graz, Graz, 8010, Austria.
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D007422:Intestines / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D064307:Microbiota; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000503:physiopathology*; D054464:Peroxiredoxins / Q000378:metabolism*; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D012336:RNA, Ribosomal, 16S; D054464:Peroxiredoxins