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Int J Clin Exp Pathol 2010;3(5):472-481

Original Article
Regulation of oxidative stress and inflammation by hepatic adiponectin receptor 2 in an
animal model of nonalcoholic steatohepatitis

Tokio Matsunami, Yukita Sato, Satomi Ariga, Takuya Sato, Haruka Kashimura, Yuki Hasegawa, Masayoshi Yukawa

Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa 252-0880,

Received May 7, 2010, accepted May, 2010, available May, 2010

Abstract: The pathogenesis of nonalcoholic steatohepatitis (NASH) is not well understood; however, the progression of fatty liver to NASH has
been linked to oxidative stress and lipid peroxidation in the liver, leading to inflammation. Although the adiponectin receptor 2 (AdipoR2) has
been identified as a modulator of oxidative stress and inflammation in the liver, it remains unclear whether the receptor has hepatic antioxidant
and anti-inflammatory effects in NASH. In this study, we used an animal model of NASH to examine hepatic AdipoR2. Obese fa/fa Zucker rats
fed a high-fat and high-cholesterol (HFC) diet spontaneously developed fatty liver with inflammation and fibrosis, characteristic of NASH, after 4,
8, or 12 weeks of HFC diet consumption. AdipoR2 expression was significantly decreased, whereas the expression of genes related to NADPH
oxidase complex were increased. As a result of the decrease in AdipoR2 expression, the mRNA expression of genes located downstream of
AdipoR2, i.e., Cu-Zn superoxide dismutase (Cu-Zn SOD) and Mn-SOD, also decreased. Furthermore, the expression of genes related to
inflammation was increased. Increased oxidative stress and inflammation by down-regulation of AdipoR2 may contribute to the progression of
NASH. Thus, the AdipoR2 might be a crucially important regulator of hepatic oxidative stress and inflammation in NASH.  (IJCEP1005002).

Key words: Nonalcoholic steatohepatitis, adiponectin receptor 2, inflammation, oxidative stress, Zucker rats

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Yukita Sato, Laboratory of Biomedical Science
Department of Veterinary Medicine
College of Bioresource Sciences
Nihon University
Fujisawa 252-0880, Japan.
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