Fig. 3

Liver lipid synthesis, accumulation and oxidation. Sources of liver fat: Dietary consumption of FAs, adipose tissue breakdown to produce FFAs, and DNL. FFAs are ultimately processed into TGs and stored as fat droplets in the liver. DNL: Palmitic acid and FAs are synthesized from glucose under the catalysis of various enzymes. ACS catalyses the formation of palmitoyl-CoA from PA via acetyl-CoA, which is extended and desaturated, respectively, under the action of ELOVL6 and SCD1. Finally, MUFAs are generated. TG synthesis: G3P and acyl-CoA synthesis by DNL is catalysed by GPAT to generate LPA. With catalysis of LPAAT, PA is generated by acylation of LPA with another acyl-CoA. PA is dephosphorylated under the catalysis of PAP to produce DAG. Finally, DAG is acylated to form TG by an acyl-CoA molecule under the catalytic activity of DGAT. FA oxidation: Acyl-CoA molecules are transported into the mitochondria by the activity of CPT1, CPT2 and CACT; the acyl-CoA molecules are then oxidized to form acetyl-CoA. VLDL synthesis: In hepatocytes, TG, cholesterol and APOB100 combine in the ER via MTP activity to form VLDL, which is released into the blood. In patients with NAFLD, hepatic steatosis can be stimulated via increased FA uptake, increased DNL, decreased VLDL secretion and decreased FA β-oxidation followed by esterification for TG synthesis