摘要：SummaryExcessive consumption of high-fructose diets is associated with insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD). However, fructose differentially affects hepatic regulation of lipogenesis in males and females. Hence, additional studies are necessary in order to find strategies taking gender disparities in fructose-induced liver damage into consideration. Although the eighth member of facilitated glucose transporters (GLUT8) has been linked to fructose-induced macrosteatosis in female mice, its contribution to the inflammatory state of NAFLD remains to be elucidated. Combining pharmacological, biochemical, and proteomic approaches, we evaluated the preventive effect of targeted liver GLUT8 silencing on liver injury in a mice female fructose-induced non-alcoholic steatohepatitis female mouse model. Liver GLUT8-knockdown attenuated fructose-induced ER stress, recovered liver inflammation, and dramatically reduced fatty acid content, in part, via the omega oxidation. Therefore, this study links GLUT8 with liver inflammatory response and suggests GLUT8 as a potential target for the prevention of NAFLD.Graphical abstractDisplay OmittedHighlights•Liver injury induced by high-fat or fructose diet occurs through different mechanisms•Fructose increases inflammatory responses and activates pathological ER stress•Liver-specific GLUT8 knockdown ameliorates fructose-induced injury•GLUT8 knockdown increased lipid mobilization partially driven by omega oxidationBiological sciences; physiology; endocrinology
