Fig. 3

Glucose and fructose metabolism in non-alcoholic fatty liver disease (NAFLD). a Increases in glucose transport results in enhanced glycolysis in the liver. There, pyruvate is converted to oxaloacetate, which provides more substrates for de novo lipogenesis (DNL), or lactate, which stimulates the DNL pathway via decreased activity of histone deacetylase (HDAC) [223]. b In addition, fructose is phosphorylated to fructose-1-phosphate (F-1-P) by ketohexokinase (KHK) upon entering hepatocytes, which have high-rate activity and bypass more limited steps [224]. Moreover, substrates, such as adenosine diphosphate (ADP) derived from adenosine triphosphate (ATP) during hydrolysis activity, are converted into uric acid, which impairs the liver by stimulating DNL [225, 226]. c Insulin regulates the liver directly by upregulating sterol regulatory element-binding protein 1c (SREBP1c) and carbohydrate-responsive element-binding protein (ChREBP); it also decreases the production of very-low-density lipoprotein (VLDL) via the downregulation of microsomal triglyceride transfer protein (MTTP) and apolipoprotein B (ApoB) [78, 79]