Br J Pharmacol.2020 Aug;177(16)(IF:8.739).

Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non-alcoholic fatty liver disease by up-regulating the FGF21/PGC-1α pathway

Liwei Wu  1 Wenhui Mo  2 Jiao Feng  1 Jingjing Li  1   3 Qiang Yu  1 Sainan Li  1 Jie Zhang  1   4 Kan Chen  1 Jie Ji  1 Weiqi Dai  1   3   5   6   7 Jianye Wu  3 Xuanfu Xu  2 Yuqing Mao  8 Chuanyong Guo  1 Affiliations

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Background and purpose: Non-alcoholic fatty liver disease (NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Astaxanthin (Ax) is a carotenoid, and beneficial effects of astaxanthin, including anti-oxidative, anti-inflammatory, and anti-tumour activity, have been identified. The present study aimed to elucidate the protective effect of astaxanthin against NAFLD and its underlying mechanism.

Experimental approach: Mice were fed either a high fat or chow diet, with or without astaxanthin, for up to 12 weeks. L02 cells were treated with free fatty acids combined with different doses of astaxanthin for 48 h. Histopathology, expression of lipid metabolism, inflammation, apoptosis, and fibrosis-related gene expression were assessed. And the function of mitochondria was also evaluated.

Key results: The results indicated that astaxanthin attenuated HFD- and FFA-induced lipid accumulation and its associated oxidative stress, cell apoptosis, inflammation, and fibrosis both in vivo and in vitro. Astaxanthin up-regulated FGF21 and PGC-1α expression in damaged hepatocytes, which suggested an unrecognized mechanism of astaxanthin on ameliorating NAFLD.

Conclusion and implications: Astaxanthin attenuated hepatocyte damage and mitochondrial dysfunction in NAFLD by up-regulating FGF21/PGC-1α pathway. Our results suggest that astaxanthin may become a promising drug to treat or relieve NAFLD.