title: Peroxiredoxin 4 protects against nonalcoholic steatohepatitis and type 2 diabetes in a nongenetic mouse model.
abstract: OBJECTIVE
  Consumption of a high-fructose diet (HFrD) can induce the development of a metabolic syndrome, manifesting as nonalcoholic steatohepatitis (NASH) and/or type 2 diabetes mellitus (T2DM), via a process in which oxidative stress plays a critical role. Peroxiredoxin 4 (PRDX4) is a unique and only known secretory member of the PRDX antioxidant family. However, its putative roles in the development of NASH and/or T2DM have not been investigated.
  
  
  RESULTS
  To elucidate the functions of PRDX4 in a metabolic syndrome, we established a nongenetic mouse model of T2DM by feeding mice a HFrD after injecting a relatively low dose of streptozotocin. Compared with wild-type (WT), human PRDX4 transgenic (Tg) mice exhibited significant improvements in insulin resistance, characterized by a lower glucose and insulin concentration and faster responses in glucose tolerance tests. The liver of Tg also showed less severe vesicular steatosis, inflammation, and fibrosis, along with lower lipid concentrations, lower levels of oxidative stress markers, more decreased expression of hepatic aminotransferase, and more reduced stellate cell activation than those in the WT liver, reminiscent of human early NASH. Hepatocyte apoptosis was also significantly repressed in Tg mice. By contrast, serum adiponectin levels and hepatic adiponectin receptor expression were significantly lower in WT mice, consistent with greater insulin resistance in the peripheral liver tissue compared with Tg mice.
  
  
  CONCLUSIONS
  Our data for the first time show that PRDX4 may protect against NASH, T2DM, and the metabolic syndrome by ameliorating oxidative stress-induced injury.
authors.affiliation: 1 Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health , Kitakyushu, Japan .
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nabeshima
authors.forename: Sohsuke
authors.initials: S
authors.lastname: Yamada
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Wang
authors.forename: Shohei
authors.initials: S
authors.lastname: Shimajiri
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Tasaki
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Noguchi
authors.forename: Shohei
authors.initials: S
authors.lastname: Kitada
authors.forename: Teruo
authors.initials: T
authors.lastname: Watanabe
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000276:immunology; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000201:enzymology* / Q000276:immunology; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000502:physiology*; D054419:Receptors, Adiponectin / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D000447:Aldehydes; D018836:Inflammation Mediators; D054419:Receptors, Adiponectin; D017392:Thiobarbituric Acid Reactive Substances; D006151:Guanosine; C046215:8-hydroxyguanosine; D054464:Peroxiredoxins; C515981:Prdx4 protein, mouse; C027576:4-hydroxy-2-nonenal