Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E.
Yinhua Ni,Mayumi Nagashimada,Fen Zhuge,Lili Zhan,Naoto Nagata,Akemi Tsutsui,Yasuni Nakanuma,Shuichi Kaneko,Tsuguhito Ota +8 more
TL;DR: Overall, astaxanthin was more effective at both preventing and treating NASH compared with vitamin E in mice, and improved hepatic steatosis and tended to ameliorate the progression of NASH in biopsy-proven human subjects, suggesting that astxanthin might be a novel and promising treatment for NASH.
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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.
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The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Konstantin Kazankov,Simon Mark Dahl Jørgensen,Karen Louise Thomsen,Holger Jon Møller,Hendrik Vilstrup,Jacob George,Detlef Schuppan,Detlef Schuppan,Henning Grønbæk +8 more
TL;DR: Experimental and clinical data support a central role for macrophages in the development and progression of nonalcoholic fatty liver disease (NAFLD) and non alcoholic steatohepatitis (NASH) and studies investigating drugs that target macrophage recruitment to the liver, Macrophage polarization and their inflammatory effects as potential treatment options for patients with NASH are reviewed.
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Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments
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