Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E.
Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E.
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DOI：
10.1038/srep17192
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发表时间：
2015-11-25
影响因子：
4.6
通讯作者：
Ota T
中科院分区：
文献类型：
--
作者：
Ni Y;Nagashimada M;Zhuge F;Zhan L;Nagata N;Tsutsui A;Nakanuma Y;Kaneko S;Ota T
肝脏脂质过度蓄积和过氧化反应可导致肝脏胰岛素抵抗和非酒精性脂肪性肝炎（NASH）。维生素E已成为NASH的标准治疗方法。然而，虾青素，一种抗氧化剂类胡萝卜素，比维生素E更有效地抑制脂质过氧化。在这里，我们比较了虾青素和维生素E在NASH中的作用。我们首先证明了虾青素改善遗传（ob/ob）和高脂饮食诱导的肥胖小鼠的肝脏脂肪变性。在NASH的脂毒性模型中：喂食高胆固醇和高脂肪饮食的小鼠，虾青素减轻了过度的肝脏脂质积累和过氧化，增加了M1型巨噬细胞/枯否细胞的比例，并激活了星状细胞，以改善肝脏炎症和纤维化。此外，虾青素引起巨噬细胞/枯否细胞中的M2-显性转变，以及随后肝脏中CD 4+和CD 8 + T细胞募集的减少，这有助于改善胰岛素抵抗和肝脏炎症。重要的是，虾青素可以逆转既存NASH的胰岛素抵抗以及肝脏炎症和纤维化。总的来说，在小鼠中，与维生素E相比，虾青素在预防和治疗NASH方面更有效。此外，虾青素改善肝脂肪变性，并倾向于改善活检证实的人类受试者中NASH的进展。这些结果表明，虾青素可能是一种新的和有前途的治疗NASH。
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.