Beraprost sodium, a prostacyclin analogue, reduces fructose-induced hepatocellular steatosis in mice and in vitro via the microRNA-200a and SIRT1 signaling pathway

Abstract Purpose To determine whether beraprost sodium, a prostacyclin analogue, could reduce hepatic lipid accumulation induced by fructose in mice and cultured human hepatocytes, and to investigate the expression of microRNAs and the sirtuin 1 (SIRT1) pathway. Methods Male C57BL/6JNju mice were divided into three groups and fed one of the following diets: a normal diet, a high fructose diet, or a high fructose diet with beraprost sodium treatment. In addition, human-derived HepG2 cells were cultured and treated with fructose (25 mmol/L) with or without beraprost sodium (10 μmol/L) for 24 h, and transfected with small interfering RNA (siRNA) against SIRT1, miR-200a mimic, or miR-200a inhibitor for 48 h. The miRNA microarray analysis was performed on the HepG2 cells, and the expression profiles of miRNAs were analyzed using Gene Cluster 3.0 and verified using qPCR. Results Beraprost sodium treatment attenuated hepatic steatosis, induced the transcription of genes involved in lipid metabolism in C57BL/6 mice (P  Conclusions Our study demonstrated that SIRT1 pathway mediated the effects of beraprost sodium on attenuation of hepatic lipid disorders induced by fructose and revealed the primary role of miR-200a in the regulation of hepatic SIRT1 by beraprost sodium. Our findings suggested that SIRT1 might be a therapeutic target of fructose-related metabolism disorders.