Figure 4.

GGPPS regulates NAFLD-HCC progression by determining the hepatic glucose/fatty acid preference under fat overload. Short-term HFD overload increases GGPPS expression and triggers a change in the prenylation pattern favoring GGPP synthesis (9), leading to increased glycolysis and DNL. However, long-term HFD overload decreases GGPPS expression and disrupts the FPP and GGPP balance so as to unbalance the ratio of farnesylated proteins and geranylgeranylated proteins, which drives the Warburg effect through metabolic reprogramming favoring glycolysis to exacerbate fibrosis (4).