Acot12 is a cytosolic enzyme that catalyzes the hydrolysis of acetyl-CoA into acetate plus CoASH. In addition to its enzymatic domains, Acot12 also contains a steroidogenic acute regulatory protein-related lipid transfer (START) domain, which functions as lipid sensor. Acot12 activity in the liver suppresses both glucose production and lipogenesis. Increased rates of hepatocellular fatty acid uptake and oxidation presumably reflect compensatory mechanisms directed towards the repletion of TCA cycle intermediates that support glucose and lipid biosynthesis. We speculate that Acot12 regulates hepatic nutrient metabolism by controlling cytosolic acetyl-CoA concentrations within the liver.