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.