Lactate and Ketone Bodies Act as Energy Substrates as Well as Signal Molecules in the Brain

Abstract

Astroglia or astrocytes, the most abundant cells in the brain, are interposed between neuronal synapses and the microvasculature in the brain’s gray matter. This unique anatomical location allows astroglia to play pivotal roles in brain metabolism as well as in the regulation of cerebral blood flow. In particular, astroglial cellular metabolic compartmentation exerts supportive roles in dedicating neurons to the generation of action potentials and protects neurons against the oxidative stress associated with their high energy consumption. Key products of astroglia include lactate and ketone bodies (beta-hydroxybutyrate and acetoacetate), which can also be produced avidly by muscle and liver, respectively. Therefore, brain cells, skeletal muscles, and hepatocytes constitute a metabolic compartmentation in the whole body. In this chapter, I will focus on brain cells, especially astroglia, since the impairment of normal astroglial function can lead to numerous neurological disorders including stroke, neurodegenerative diseases, and neuro-immunological diseases. I will also discuss the metabolic responses of brain cells in terms of food consumption and exercise. A better understanding of the astroglial metabolic response is expected to lead to the development of novel therapeutic strategies for diverse neurological diseases.