Steiner Pascal
Société des Produits Nestlé SA, Nestlé Research, Brain Health Department, Lausanne, Switzerland,
Ann Nutr Metab. 2019;75 Suppl 1:8-18. doi: 10.1159/000508054. Epub 2020 Jun 19.
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.
在孕期和婴儿期，人类大脑发育极快；脑容量显著增加，在2 - 4周、1岁和2岁时分别达到成人大脑容量的36%、72%和83%，这对于建立神经网络以及发展认知、运动、社交和情感技能的能力至关重要，这些技能将在整个童年和成年期不断完善。大脑结构和功能的这种巨大变化与极高的能量需求相关，远远超过身体其他器官的需求。据估计，在儿童时期，大脑可能占身体基础能量需求的60%。虽然成人大脑的主要能量来源是葡萄糖，但在大脑发育期间，葡萄糖似乎不足以维持其巨大的代谢需求。最近，有人提出，大脑利用脂肪酸氧化产生的酮体（KBs）作为补充能量来源的能力解决了这一能量挑战。在此，我们首先描述随着时间推移驱动大脑发育的主要细胞和生理过程，以及不同的大脑代谢途径如何参与支持这些过程。人们认为，大多数能量底物用于支持神经元活动和信号传递。我们讨论葡萄糖和KBs如何代谢以提供用于合成脂质、核酸和胆固醇的碳骨架，这些是神经元细胞增殖不可或缺的组成部分，也用于通过突触形成/消除和髓鞘形成来建立和完善大脑连接。我们得出结论，葡萄糖和KBs不仅对支持发育中的大脑的能量需求很重要，而且它们也是大脑结构生长和重组所依赖的大分子生物合成的必需底物。我们强调，支持KBs产生的葡萄糖和脂肪酸存在于复杂的食物基质中，如母乳，了解它们的可利用性如何影响大脑将是促进充足营养以支持大脑代谢从而实现最佳大脑发育的关键。
