As with all cells in our body, I know that the brain can get fed from both glucose and ketones, so my question is, given both of them, which one would the brain prefer to utilize first?
First of all, for those readers with less knowledge of the general principles of biology, I want to state an important, even if obvious, point: The brain doesn't "prefer" anything. Despite being the smartest organ in the body, it is subjected (like any other biological system) to changes in the concentrations of the substances in question, that is, glucose and ketone bodies.
According to a study in rats from 2010, it seems that ketone bodies suppress glucose metabolism in order to conserve glucose when its concentration is too low for the body to be used regularly. Therefore, the ketone bodies are regarded as neuroprotective, since their metabolism prevents the brain cells from starving.
Another study in rats from 2013 emphasizes this point further. Please note the following excerpt from the discussion section:
The brain's ability to switch from glucose oxidation towards ketone bodies requires a type of ‘cerebral metabolic adaptation'. This process is not well understood but is thought to be highly associated with the duration and level of ketosis. Ketones are considered to supply up to 70% of the total energy demands once maximal metabolic adaptation occurs. Blood ketones become elevated during prolonged fasting or with a ketogenic diet reaching a state [of] ketosis and glucose sparing. During this process, monoca[r]boxylic transporters upregulate at the blood–brain barrier with increasing demand for ketone utilization by brain. Recently, investigators have recognized additional therapeutic properties of ketosis, such as neuroprotection after stroke or injury. What remains unclear is whether the neuroprotective or therapeutic properties of ketosis is as a result of changes in the regulation of metabolic signaling pathways...
This means that when the balance of concentrations shifts toward the ketone bodies, they will have precedence over glucose in order to conserve the latter. The mechanism is probably upregulation of ketone bodies receptors and transporters that increase its transport into the brain, as stated above.
Therefore, when the brain is given both ketone bodies and glucose (which actually happens in the fasted state - ketone bodies transport and metabolism in the brain begins when blood glucose is low, not zero), there will be "preference" for the ketone bodies, but this depends on the glucose concentration. If it shifts back, above a certain glucose concentration glucose metabolism is supposed to be renewed.