Send to:

Choose Destination
See comment in PubMed Commons below
Antioxid Redox Signal. 2013 Dec 10;19(17):1983-98. doi: 10.1089/ars.2012.4946. Epub 2013 May 3.

Peroxiredoxin 4 protects against nonalcoholic steatohepatitis and type 2 diabetes in a nongenetic mouse model.

Author information

  • 11 Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health , Kitakyushu, Japan .



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.


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.


Our data for the first time show that PRDX4 may protect against NASH, T2DM, and the metabolic syndrome by ameliorating oxidative stress-induced injury.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Mary Ann Liebert, Inc. Icon for PubMed Central
    Loading ...
    Write to the Help Desk