@article{oai:kanazawa-u.repo.nii.ac.jp:00014273,
 author = {Ni, Yinhua and Nagashimada, Mayumi and Zhuge, Fen and Zhan, Lili and Nagata, Naoto and Tsutsui, Akemi and Nakanuma, Yasuni and Kaneko, Shuichi and Ota, Tsuguhito},
 journal = {Scientific Reports},
 month = {Nov},
 note = {Hepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than Vitamin E. Here, we compared the effects of astaxanthin and Vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese mice. In a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet, astaxanthin alleviated excessive hepatic lipid accumulation and peroxidation, increased the proportion of M1-type macrophages/Kupffer cells, and activated stellate cells to improve hepatic inflammation and fibrosis. Moreover, astaxanthin caused an M2-dominant shift in macrophages/Kupffer cells and a subsequent reduction in CD4+ and CD8+ T cell recruitment in the liver, which contributed to improved insulin resistance and hepatic inflammation. Importantly, astaxanthin reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. Overall, astaxanthin was more effective at both preventing and treating NASH compared with Vitamin E in mice. Furthermore, astaxanthin improved hepatic steatosis and tended to ameliorate the progression of NASH in biopsy-proven human subjects. These results suggest that astaxanthin might be a novel and promising treatment for NASH.},
 title = {Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with Vitamin E},
 volume = {5},
 year = {2015}
}