Hepatic transcriptome profiles of mice with diet-induced nonalcoholic steatohepatitis treated with astaxanthin and vitamin E

Astaxanthin alleviates hepatic lipid accumulation and peroxidation, inflammation, and fibrosis in mice with high-cholesterol, high-cholate, and high-fat (CL) diet-induced nonalcoholic steatohepatitis (NASH). It has been proposed as a potential new treatment to inhibit the progression of NASH in humans. Therefore, we compared hepatic gene expression profiles after treatment with astaxanthin or the antioxidant vitamin E in mice with CL diet-induced NASH. Comprehensive gene expression analyses of the livers of mice fed a standard, CL, or CL diet containing astaxanthin or vitamin E for 12 weeks were performed using a DNA microarray. Both astaxanthin and vitamin E effectively improved gene expression associated with eukaryotic initiation factor-2 (EIF2) signaling, which is suppressed in NASH by endoplasmic reticulum (ER) stress in the liver. Astaxanthin but not vitamin E was predicted to suppress the actions of ligand-dependent nuclear receptors peroxisome proliferator-activated receptors (PPAR) α and PPARδ and to affect related molecules. Establishing a new therapy using astaxanthin will require elucidation of astaxanthin’s molecular action on the functions of PPARα and related molecules in the livers of mice with diet-induced NASH. 7-week-old C57BL/6J male mice were fed normal chow (CRF-1) or CL diet (60% calories from fat, 1.25% cholesterol, and 0.5% sodium cholate), CL diet containing 0.02% astaxanthin, or CL diet containing 0.02% vitamin E for 12 weeks.