Mechanism of fibroblast growth factor 1 regulating fatty liver disorder in mule ducks.

Abstract

Mule ducks tend to accumulate abundant fat in their livers via feeding, which leads to the formation of a fatty liver that is several times larger than a normal liver. However, the mechanism underlying fatty liver formation has not yet been elucidated. Fibroblast growth factor 1 (FGF1), a member of the FGF superfamily, is involved in cellular lipid metabolism and mitosis. This study aims to investigate the regulatory effect of FGF1 on lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells and elucidate the underlying molecular mechanism. Hepatocytes were induced by adding 1,500:750 µmol/L oleic and palmitic acid concentrations for 36 h, which were stimulated with FGF1 concentrations of 0, 10, 100, and 1000 ng/mL for 12 h. The results showed that FGF1 significantly reduced the hepatic lipid droplet deposition and triglyceride content induced by complex fatty acids; it also reduced oxidative stress; decreased reactive oxygen species fluorescence intensity and malondialdehyde content; upregulated the expression of antioxidant factors nuclear factor erythroid 2 related factor 2 (Nrf2), HO-1, and NQO-1; significantly enhanced liver cell activity; promoted cell cycle progression; inhibited cell apoptosis; upregulated cyclin-dependent kinase 1 (CDK1) and BCL-2 mRNA expression; and downregulated Bax and Caspase-3 expression. In addition, FGF1 promoted AMPK phosphorylation, activated the AMPK pathway, upregulated AMPK gene expression, and downregulated the expression of SREBP1 and ACC1 genes, thereby alleviating excessive fat accumulation in liver cells induced by complex fatty acids. In summary, FGF1 may alleviate lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells by activating the AMPK signaling pathway.