CNS metabolism Neuronal activity accounts for 80% of the brain’s energy consumption. Blood-borne glucose is an essential energy source for the adult human brain. Both neurons and astrocytes take up glucose via the cell-specific transporters GLUT1 and GLUT3. Upon increased demand neurons ability to take up glucose is limited and lactate provided by astrocytes becomes the primary oxidative fuel. Under certain conditions the brain can also utilize acetoacetate, b-hydroxybutyrate and acetone (ketone bodies) derived from fatty acids as alternative energy source. Neurons metabolize ketone bodies to Acetyl-CoA, which is further oxidized through the TCA cycle. High circulating levels of ketone bodies are known to protect the brain. Ketone bodies also prevent seizures in GLUT1 difficiency syndrome and are important for brain development, but cellular and molecular mechanisms underlying the protective effect of ketone bodies are not yet fully clear. In the following I discuss the presumable link of metabolism with epigenetic changes and implications in brain function.