Nehlig Astrid
INSERM U 405, Faculty of Medicine, 11, rue Humann, 67085 Strasbourg Cedex, France.
Prostaglandins Leukot Essent Fatty Acids. 2004 Mar;70(3):265-75. doi: 10.1016/j.plefa.2003.07.006.
As a consequence of the high fat content of maternal milk, the brain metabolism of the suckling rat represents a model of naturally occurring ketosis. During the period of lactation, the rate of uptake and metabolism of the two ketone bodies, beta-hydroxybutyrate and acetoacetate is high. The ketone bodies enter the brain via monocarboxylate transporters whose expression and activity is much higher in the brain of the suckling than the mature rat. beta-Hydroxybutyrate and acetoacetate taken up by the brain are efficiently used as substrates for energy metabolism, and for amino acid and lipid biosynthesis, two pathways that are important for this period of active brain growth. Ketone bodies can represent about 30-70% of the total energy metabolism balance of the immature rat brain. The active metabolism of ketone bodies in the immature brain is related to the high activity of the enzymes of ketone body metabolism. Thus, the use of ketone bodies by the immature rodent brain serves to spare glucose for metabolic pathways that cannot be fulfilled by ketones such as the pentose phosphate pathway mainly. The latter pathway leads to the biosynthesis of ribose mandatory for DNA synthesis and NADPH which is not formed during ketone body metabolism and is a key cofactor in lipid biosynthesis. Finally, ketone bodies by serving mainly biosynthetic purposes spare glucose for the emergence of various functions such as audition, vision as well as more integrated and adapted behaviors whose appearance during brain maturation seems to critically relate upon active glucose supply and specific regional increased use.
由于母乳中脂肪含量高，哺乳大鼠的脑代谢代表了一种自然发生的酮症模型。在哺乳期，两种酮体β-羟基丁酸酯和乙酰乙酸的摄取和代谢速率很高。酮体通过单羧酸转运蛋白进入大脑，其在哺乳大鼠大脑中的表达和活性远高于成年大鼠。大脑摄取的β-羟基丁酸酯和乙酰乙酸被有效地用作能量代谢以及氨基酸和脂质生物合成的底物，这两条途径对这一脑快速生长时期很重要。酮体可占未成熟大鼠脑总能量代谢平衡的30%-70%。未成熟脑内酮体的活跃代谢与酮体代谢酶的高活性有关。因此，未成熟啮齿动物大脑对酮体的利用有助于节省葡萄糖，用于酮体无法满足的代谢途径，主要是磷酸戊糖途径。后一途径导致DNA合成必需的核糖以及酮体代谢过程中不产生的NADPH的生物合成，NADPH是脂质生物合成中的关键辅因子。最后，酮体主要用于生物合成目的，从而节省葡萄糖，以支持各种功能的出现，如听觉、视觉以及更综合和适应性更强的行为，这些功能在脑成熟过程中的出现似乎与活跃的葡萄糖供应和特定区域的使用增加密切相关。
