Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E

• Published in: Scientific reports Vol. 5; no. 1; p. 17192
• Main Authors: Ni, Yinhua, Nagashimada, Mayumi, Zhuge, Fen, Zhan, Lili, Nagata, Naoto, Tsutsui, Akemi, Nakanuma, Yasuni, Kaneko, Shuichi, Ota, Tsuguhito
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.11.2015; Nature Publishing Group
• Subjects: 13/1; 13/31; 13/51; 14/63; 64/60; 692/163/2743/2037; 692/4020/4021/1607/2751; Animals; Antioxidants - pharmacology; Antioxidants - therapeutic use; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Diet, High-Fat; Disease Models, Animal; Female; Glucose Metabolism Disorders - drug therapy; Humanities and Social Sciences; Humans; Insulin Resistance; Kupffer Cells - metabolism; Lipid Peroxidation - drug effects; Liver - immunology; Liver - metabolism; Liver - pathology; Macrophages - cytology; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Obese; multidisciplinary; Non-alcoholic Fatty Liver Disease - drug therapy; Science; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; Vitamin E - pharmacology; Vitamin E - therapeutic use; Xanthophylls - pharmacology; Xanthophylls - therapeutic use
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep17192

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.