Regulation of oxidative stress and inflammation by hepatic adiponectin receptor 2 in an animal model of nonalcoholic steatohepatitis.
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.
Matsunami
Tokio
T
Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University Fujisawa 252-0880, Japan.
Sato
Yukita
Y
Ariga
Satomi
S
Sato
Takuya
T
Kashimura
Haruka
H
Hasegawa
Yuki
Y
Yukawa
Masayoshi
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D020869:Gene Expression Profiling; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker; D054419:Receptors, Adiponectin; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000975:Antioxidants; D054419:Receptors, Adiponectin; C506573:adiponectin receptor 2, rat