Brain Fuel Utilization in the Developing Brain

Abstract

During pregnancy and infancy, the human brain is growing extremely fast; the brain volume increases significantly, reaching 36, 72, and 83% of the volume of adults at 2–4 weeks, 1 year, and 2 years of age, respectively, which is essential to establish the neuronal networks and capacity for the development of cognitive, motor, social, and emotional skills that will be continually refined throughout childhood and adulthood. Such dramatic changes in brain structure and function are associated with very large energetic demands exceeding by far those of other organs of the body. It has been estimated that during childhood the brain may account for up to 60% of the body basal energetic requirements. While the main source of energy for the adult brain is glucose, it appears that it is not sufficient to sustain the dramatic metabolic demands of the brain during its development. Recently, it has been proposed that this energetic challenge is solved by the ability of the brain to use ketone bodies (KBs), produced from fatty acid oxidation, as a complement source of energy. Here, we first describe the main cellular and physiological processes that drive brain development along time and how different brain metabolic pathways are engaged to support them. It has been assumed that the majority of energetic substrates are used to support neuronal activity and signal transmission. We discuss how glucose and KBs are metabolized to provide the carbon backbones used to synthesize lipids, nucleic acid, and cholesterol, which are indispensable building blocks of neuronal cell proliferation and are also used to establish and refine brain connectivity through synapse formation/elimination and myelination. We conclude that glucose and KBs are not only important to support the energy needs of the brain under development, but they are also essential substrates for the biosynthesis of macromolecules underlying structural brain growth and reorganization. We emphasize that glucose and fatty acids supporting the production of KBs are provided in complex food matrices, such as breast milk, and understanding how their availability impacts the brain will be key to promote adequate nutrition to support brain metabolism and, therefore, optimal brain development.

Glycolytic Metabolism, Brain Resilience, and Alzheimer’s Disease

“…The human brain contains an average of more than two hundred billion cells, one quadrillion connections, 100 km of nerve fibers, and 600 km of blood vessels ( Steiner, 2019 ). Therefore, it is not surprising that a brain demands an outstanding amount of energy and building blocks to maintain its highly dynamic homeostasis.…”

Milk Fatty Acid Profiles in Different Animal Species: Focus on the Potential Effect of Selected PUFAs on Metabolism and Brain Functions

“…The brain requires an outstanding energy supply to maintain its dynamic abilities and its complex architecture. Indeed, the adult brain, which accounts for about 2% of body weight, utilizes 20% of the oxygen and 20-25% of the glucose [151]. In addition, the huge brain size expansion during the first few years of life requires specific nutrients, such as lipids, proteins, and micronutrients, which are also necessary to support neuronal connectivity and brain cognitive functions in adulthood.…”

The Effect of Partly Replacing Vegetable Fat with Bovine Milk Fat in Infant Formula on Postprandial Lipid and Energy Metabolism: A Proof‐of‐principle Study in Healthy Young Male Adults

“…Bovine milk fat addition also increased serum concentrations of ketone bodies. Ketone bodies are an important energy substrate for brain development, [ 58 ] and this observation may thus bear physiological relevance. However, as this was a short‐term study in adults, giving an indication what can be expected in infants, the true acute and longer‐term effect in infants cannot be directly extrapolated from these findings and needs further studies.…”