Ketone bodies (KBs) are an energy source utilised by mammals, the terminal oxidation of which (termed ketogenesis) is most active during fasting states or starvation. This process normally occurs in the mitochondria of cells. Cytoplasmic de novo lipogenesis and cholesterol synthesis are nonoxidative metabolic fates of ketone bodies. Acetoacetyl-CoA synthetase (AACS) mediates the activation of acetoacetate (ACA) to the KB acetoacetyl-CoA (ACA-CoA) in the cytosol of cells of lipogenic tissues (Aquilo et al. 2010). AACS is proposed to provide an alternative supply of acetyl units from that of mitochondrial ketogenesis for de novo lipogenesis and cholesterol synthesis in the brain, based on rat experiments (Endemann et al. 1982, review Cotter et al. 2013). Human AACS mRNA is abundant in the kidney, heart and brain, but low in liver (Ohgami et al. 2003).