Fatty acid metabolism and acyl-CoA synthetases in the liver-gut axis

Figure 2 The crosslink between acyl-CoA synthetases and short-chain fatty acids. In mitochondria, acetyl-CoA is generated either from fatty acid β-oxidation and glucose via pyruvate or SCFAs through ACSS1 and ACSS3; acetyl-CoA is directed into energy production through the TCA cycle and electron respiration chain, as well as reflux into cytosol via citrate and again synthesizes acetyl-CoA. In addition, excessive acetate and butyrate synthesize into ketone bodies and are released into cytosol. In cytosol, acetyl-CoA is produced from pyruvate which is from both glucose and propionate; the source of acetyl-CoA can be converted from butyrate and acetate via butyryl-CoA/acetate CoA-transferase and ACSS2 respectively; cytosolic ketone bodies can also either produce acetyl-CoA or enter the blood circulation in the whole body. On the other hand, acetyl-CoA is involved in cholesterol biosynthesis. In the nucleus, acetate synthesizes acetyl-CoA via ACSS2 which is responsible for chromosome stability through histone acylation regulation. Cyto: Cytoplasma; Mito: mitochondria; Nucl: Nucleus; TCA: tricarboxylic acid cycle.