Fig. 2

Hepatic de novo lipogenesis and TG secretion. The DNL process begins with the conversion of acetyl-CoA into malonyl-CoA by ACC. Malonyl-CoA is condensed with several acetyl-CoA moieties by FASN to produce a 16-carbon palmitic acyl-CoA. Three fatty acyl-CoAs are bound to a glycerol backbone to form one TG. Glucose and fructose are taken up by the hepatocyte and may be metabolized to pyruvate for energy formation in the mitochondrial or to glycerol-3-phospate for TG synthesis. Glucose can also be stored as glycogen within the liver cell. TG are combined with apoB and packaged into VLDL for secretion into the blood stream. Malonyl-CoA, also inhibits CPT1, suppressing fatty acid uptake into the mitochondria and β-oxidation. Dietary fatty acids are also taken up by the hepatocyte and converted to fatty acyl-CoA which can be oxidized or used for TG synthesis (not shown). Stable isotope labels such as ¹³C-acetate and ²H₂O are used to determine the rate of DNL through the incorporation into VLDL-palmitate. ACC, acetyl-CoA carboxylase; ACS, acetyl-CoA synthase; ApoB, apolipoprotein B; CPT1, carnitine palmitoyl transferase 1; DHAP, dihydroxyacetone phosphate; FASN, fatty acid synthase; GA-3-P, glyceraldehyde-3-phosphate; P, phosphate; TCA, the citric acid cycle; TG, triglyceride; VLDL, very low density lipoprotein