Astaxanthin Attenuates Hepatic Damages and Mitochondrial Dysfunction in Nonalcoholic Fatty Liver Disease by Regulating the FGF21/PGC-1α Pathway

Abstract

Backgrounds: Non-alcoholic fatty liver disease(NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. The pathogenesis of NAFLD is described as the two-hit theory. However, the underlying mechanisms remains to be fully explored. Beneficial effects of astaxanthin(Ax) have been identified,including anti-oxidative, anti-inflammatory, and anti-tumor activity. The present study aimed to elucidate the protective effect of Ax against NAFLD and its underlying mechanism. Methods: Mice were fed either a high fat or control diet, with or without AX, for up to 12 weeks. L02 cells were treated with free fatty acids combined with different doses of Ax for 48 h. Histopathology, expression of lipid metabolism, inflammation, apoptosis, and fibrosis-related genes were assessed. Findings: The results indicated that Ax attenuated HFD- and FFA-induced lipid accumulation and its associated oxidative stress, cell apoptosis, inflammation, and fibrosis both in vivo and in vitro. Ax upregulated FGF21 and PGC-1α expression in damaged hepatocytes, which suggested an unrecognized mechanism of Ax on ameliorating NAFLD. Interpretation: Ax attenuated hepatocyte damage and mitochondrial dysfunction in NAFLD by upregulating FGF21/PGC-1α.Our studies verified that Ax may become a promising drug to treat or relieve NAFLD. Funding: Work was supported by the National Natural Science Foundation of China (NO: 81670472, 81700502 and 81800538); National Natural Science Foundation of Shanghai (NO: 19ZR1447700); the Health System Innovation Plan of Shanghai Putuo District Science and Technology Committee (NO: PTKWWS2018001); the WBN Liver Disease Research Fund of China Hepatitis Prevention Foundation (NO: CFHPC2019031); the Yangfan Plan of Shanghai Science and Technology Commission (NO: 2018YF1420000); the Project of Shanghai Health Commission (NO: 2019469). Declaration of Interest: The authors have declared that no competing interest exists. Ethical Approval: Experimental protocols were approved by the Animal Care and Use Committee of Shanghai Tongji University, China. All animal experiments were carried out according to the guidelines of the China National Institutes of Health. All efforts were made to minimize suffering of experimental mice in this research.