Knockdown of hepatic aquaglyceroporin-9 alleviates high fat diet-induced non-alcoholic fatty liver disease in rats

Non-alcoholic fatty liver disease (NAFLD) has emerged as a common public health problem that can progress to end-stage liver disease. Although the function of aquaglyceroporin-9 (AQP9) as a glycerol channel has been proven, the mechanism of AQP9 in the development of NAFLD is poorly understood. To investigate the effect of hepatic glycerol uptake inhibition, we utilized a lentivirus-associated RNA interference technique to knock down the expression of hepatic AQP9 in high fat diet (HFD)-induced NAFLD in rodents. Male Sprague-Dawley rats were fed with a standard chow diet or HFD for 8 weeks. Rats fed a HFD were separated into 3 groups: HFD, control and transfection group, which were injected with equivalent amounts of PBS, lentivirus-scramble and lentivirus-shRNA-AQP9 through the hepatic portal vein. The results showed a remarkable decrease in the expression of AQP9 mRNA and protein in liver for the transfection group. Furthermore, less hepatic steatosis occurred when compared to the HFD and control groups after 8 weeks. Our results indicate a potential role for AQP9 in the pathogenesis of hepatic steatosis.

► AQP9-shRNA lentiviral effectively down-regulated AQP9 mRNA and protein expression in hepatic tissues. ► Knockdown of AQP9 expression alleviated hepatic steatosis. ► Knockdown of AQP9 expression improved intrahepatic lipid accumulation, but exacerbated serum lipids levels.