PMID- 23477499
OWN - NLM
STAT- MEDLINE
DCOM- 20140728
LR  - 20240109
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Print)
IS  - 1523-0864 (Linking)
VI  - 19
IP  - 17
DP  - 2013 Dec 10
TI  - Peroxiredoxin 4 protects against nonalcoholic steatohepatitis and type 2 diabetes 
      in a nongenetic mouse model.
PG  - 1983-98
LID - 10.1089/ars.2012.4946 [doi]
AB  - AIMS: 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. INNOVATION AND CONCLUSION: 
      Our data for the first time show that PRDX4 may protect against NASH, T2DM, and 
      the metabolic syndrome by ameliorating oxidative stress-induced injury.
FAU - Nabeshima, Atsunori
AU  - Nabeshima A
AD  - 1 Department of Pathology and Cell Biology, School of Medicine, University of 
      Occupational and Environmental Health , Kitakyushu, Japan .
FAU - Yamada, Sohsuke
AU  - Yamada S
FAU - Guo, Xin
AU  - Guo X
FAU - Tanimoto, Akihide
AU  - Tanimoto A
FAU - Wang, Ke-Yong
AU  - Wang KY
FAU - Shimajiri, Shohei
AU  - Shimajiri S
FAU - Kimura, Satoshi
AU  - Kimura S
FAU - Tasaki, Takashi
AU  - Tasaki T
FAU - Noguchi, Hirotsugu
AU  - Noguchi H
FAU - Kitada, Shohei
AU  - Kitada S
FAU - Watanabe, Teruo
AU  - Watanabe T
FAU - Fujii, Junichi
AU  - Fujii J
FAU - Kohno, Kimitoshi
AU  - Kohno K
FAU - Sasaguri, Yasuyuki
AU  - Sasaguri Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130503
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Adiponectin)
RN  - 0 (Adipoq protein, mouse)
RN  - 0 (Aldehydes)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, Adiponectin)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 12133JR80S (Guanosine)
RN  - 3868-31-3 (8-hydroxyguanosine)
RN  - EC 1.11.1.15 (Peroxiredoxins)
RN  - EC 1.11.1.15 (Prdx4 protein, mouse)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
MH  - Adiponectin/metabolism
MH  - Aldehydes/metabolism
MH  - Animals
MH  - Apoptosis
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Experimental/*enzymology/immunology
MH  - Diabetes Mellitus, Type 2/*enzymology/immunology
MH  - Disease Models, Animal
MH  - Fatty Liver/*enzymology/immunology
MH  - Guanosine/analogs & derivatives/metabolism
MH  - Hepatocytes/physiology
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Liver/enzymology/immunology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Non-alcoholic Fatty Liver Disease
MH  - Oxidative Stress
MH  - Peroxiredoxins/*physiology
MH  - Receptors, Adiponectin/metabolism
MH  - T-Lymphocytes/immunology
MH  - Thiobarbituric Acid Reactive Substances/metabolism
PMC - PMC3869472
EDAT- 2013/03/13 06:00
MHDA- 2014/07/30 06:00
PMCR- 2013/12/10
CRDT- 2013/03/13 06:00
PHST- 2013/03/13 06:00 [entrez]
PHST- 2013/03/13 06:00 [pubmed]
PHST- 2014/07/30 06:00 [medline]
PHST- 2013/12/10 00:00 [pmc-release]
AID - 10.1089/ars.2012.4946 [pii]
AID - 10.1089/ars.2012.4946 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2013 Dec 10;19(17):1983-98. doi: 10.1089/ars.2012.4946. 
      Epub 2013 May 3.