Fig. 1.

Overview of the de novo lipogenesis pathway. Dietary glucose undergoes a series of reactions of glycolysis to generate pyruvate. Pyruvate enters mitochondria to be used in the tricarboxylic acid (TCA) cycle to produce energy and form citrate. After transported back to the cytoplasm, citrate is converted to acetyl-CoA by the action of ATP-citrate lyase (ACLY). Acetyl-CoA is subsequently converted to malonyl-CoA, which is utilized for the 16-carbon saturated palmitate synthesis by fatty acid synthase (FASN) activity. Stearoyl-CoA desaturase (SCD) converts saturated fatty acids to monounsaturated fatty acids. Regulation of de novo lipogenesis (DNL) is mainly mediated by sterol regulatory element-binding protein-1 (SREBP-1), which activates DNL enzymes’ expression, including ACLY, ACC, FASN, and SCD. Based on the TCGA LIHC database, these enzymes (labeled in red) are significantly upregulated at the transcriptional level in liver cancer compared with matched adjacent nontumorous tissues. TCGA LIHC, The Cancer Genome Atlas Liver Hepatocellular Carcinoma.