Fig. 4. Influence of Bach1−/− ablation on hepatic fibrogenesis. (A) Liver sections from wild type (A and B) and Bach1−/− mice (C and D) fed either regular chow (left panels) or MCD diet (right panels) were processed for AzanMallory staining. (original magnification 200 ×). (B) Following 4 w of either regular chow or MCD diet, hepatic mRNA expressions of αSMA were quantified (n = 5/each group) by quantitative realtime PCR. * p<0.05, regular chow vs MCD diet. †p<0.05, wild type (open bar) vs Bach1−/− mice (closed bar). In conclusion, Bach1−/− mice are resistant to the development of hepatic steatohepatitis with concomitant induction of HO-1 in MCD diet-induced NASH model. Reduced steatosis in Bach1−/− mice following MCD diet might be attributable to preserved expressions of PPARα and MTP that play an important role in hepatic fatty acid oxidation and triglyceride secretion respectively. Hepatic levels of MDA, a biomarker of oxidative stress, as well as serum ALT, an indicator of liver injury were significantly decreased Bach1−/− mice compared to wild type mice, suggesting anti-oxidative effect of HO-1 induction in the absence of Bach1. Since oxidative stress, the second hit in NASH pathogenesis causes impairment of cellular bioenergetics leading to further disruption of hepatic lipid metabolism, abatement of oxidative stress by Bach1 inhibition might be one of therapeutic strategies for the treatment of NASH/NAFLD. M. Inoue et al. Acknowlegment This study was supported by a Grant-in-aid from the Ministry of Health, Labor and Welfare of Japan to S. Tazuma (Grant number: H20-Nanchi-Ippan-025). Abbreviations HO heme oxygenase NASH nonalcoholic steatohepatitis MCD diet methionine-choline deficient diet PPARα peroxisome proliferator-activated receptor α MTP microsomal triglyceride transfer protein MDA malondialdehyde ALT alanine aminotransferase NAFLD nonalcoholic fatty liver disease CO carbon monoxide J. Clin. Biochem. Nutr. | March 2011 | vol. 48 | no. 2 | 165 ©2011 JCBN