学術雑誌論文 Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with Vitamin E

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

5p.17192 , 2015-11-25 , Nature Publishing Group
ISSN:2045-2322
内容記述
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.
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http://dspace.lib.kanazawa-u.ac.jp/dspace/bitstream/2297/43909/1/ME-PR-OTA-T-17192.pdf

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