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

Abstract

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.

• Authors: Yinhua Ni, Mayumi Nagashimada, Fen Zhuge, Lili Zhan, Naoto Nagata, Akemi Tsutsui, Yasuni Nakanuma, Shuichi Kaneko, Tsuguhito Ota
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 17192 (Nov 25 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26603489 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Srebf1 protein, mouse
• Sterol Regulatory Element Binding Protein 1
• Xanthophylls
• Vitamin E
• astaxanthine

Topics

• Animals
• Antioxidants (pharmacology, therapeutic use)
• CD4-Positive T-Lymphocytes (cytology, immunology)
• CD8-Positive T-Lymphocytes (cytology, immunology)
• Diet, High-Fat
• Disease Models, Animal
• Female
• Glucose Metabolism Disorders (drug therapy)
• Humans
• Insulin Resistance
• Kupffer Cells (metabolism)
• Lipid Peroxidation (drug effects)
• Liver (immunology, metabolism, pathology)
• Macrophages (cytology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Non-alcoholic Fatty Liver Disease (drug therapy)
• Sterol Regulatory Element Binding Protein 1 (genetics, metabolism)
• Vitamin E (pharmacology, therapeutic use)
• Xanthophylls (pharmacology, therapeutic use)