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

フォーマット:

論文

責任表示:

Ni, Yinhua ; Nagashimada, Mayumi ; Zhuge, Fen ; Zhan, Lili ; Nagata, Naoto ; Tsutsui, Akemi ; Nakanuma, Yasuni ; Kaneko, Shuichi ; Ota, Tsuguhito

言語:

英語

出版情報:

Nature Publishing Group, 2015-11-25

著者名:

Ni, Yinhua

Nagashimada, Mayumi

Zhuge, Fen

Zhan, Lili

Nagata, Naoto

Tsutsui, Akemi

Nakanuma, Yasuni

Kaneko, Shuichi

Ota, Tsuguhito

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掲載情報:

Scientific Reports

ISSN:

2045-2322      

巻:

5

開始ページ:

17192

バージョン:

publisher

概要:

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. 続きを見る

URL:

http://hdl.handle.net/2297/43909