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

Abstract

Introduction: Non-alcoholic fatty liver disease(NAFLD) is considered to be one of the most common chronic liver diseases across worldwide. Inflammation, cell apoptosis and fibrogenesis are all typical lipotoxicity-associated changes during NAFLD. 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. Method: 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. Results: 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. Conclusions: Ax prevented hepatic triglyceride accumulation,and attenuated hepatocyte damage and mitochondrial dysfunction.And Ax decreased the severity of experimental steatohepatitis via mechanisms likely to involve the up-regulation of FGF21/PGC-1α.