Food for Thought: What Fuels Brain Cells? (2013)

The brain is a thrifty organ. It requires only 20 Watts, much like a basic household light bulb to fuel its amazing information processing power. This energetic cost is amazingly low when compared to the Megawatts required by today’s most powerful supercomputers, whose performance, particularly in terms of flexibility and learning capacities, pales when compared to the human brain. Yet, as far as the body’s energetic budget goes, the brain is a glutton. While representing only 2% of the body mass, 15% of the blood pumped by the heart is delivered to the brain. From the blood, the brain extracts 20% of the “stuff” that fuels all cells of the body, namely glucose (sugar) and oxygen. This value means that the brain uses per unit mass, ten times more energy than the rest of the organism. What is it that is so costly in brain function compared to the other organs of the body? It is that energy is used to constantly “recharge the batteries” of neurons, the information processing units of the brain. The signaling mechanisms between neurons necessary for information processing represent approximately 90% of the energy used by the brain. In neurons, signaling is based on the rapid flow of charges — carried by ions such as sodium, potassium and calcium across the membranes of the dendrites and the soma. This does not cost much per se, as this flow of ions follows favorable gradients; however re-establishing – recharging-these constantly dissipated gradients is the main energy-consuming process of the brain. In recent years, thanks to the development of new imaging technologies such as positron emission tomography (PET) and functional Magnetic Resonance Imaging (fMRI) and in vivo biochemical approaches such as magnetic resonance spectroscopy (MRS), it became apparent that the brain can use molecules other than glucose to produce energy. And the use of glucose itself may be more complex than initially thought. With these techniques it is possible to follow the metabolic fate of specifically-labeled molecules and identify energy substrates other than glucose that can provide an alternative fuel to brain cells. One such alternative fuel is lactate, a byproduct of glucose, which is formed by muscles during sustained physical exercise. Under such conditions, the human brain takes up and uses lactate as a fuel, which can supply up to 20% of the total brain energy demands. Lactate infusions have the same effect. In both conditions increased plasma lactate results in a decrease in glucose utilization by the brain, raising the possibility that lactate is preferentially used by neurons over glucose as an energy source. In fact, even under basal conditions the brain extracts 10% of its energy demands from plasma lactate. Another, energy substrate that can be used by the brain is acetate. Acetate can be formed from alcohol in the liver through two enzymatic steps. Alcohol intake decreases glucose utilization and increases acetate uptake by the brain, suggesting, as shown for lactate, the use of acetate as an alternative fuel for the brain. Interestingly, a recent MRS study using labelled acetate has revealed that in heavy alcohol drinkers the brain markedly increases its capacity to take up acetate and to use it as an energy fuel. The reported changes in brain energy metabolism induced by chronic alcohol intake may have important ramifications for the understanding of alcohol dependence and the management of chronic alcohol abuse.