Edmond J, Higa T A, Korsak R A, Bergner E A, Lee W N
Department of Biological Chemistry and the Mental Retardation Research Center, UCLA School of Medicine, Los Angeles, California 90095-1737, USA.
J Neurochem. 1998 Mar;70(3):1227-34. doi: 10.1046/j.1471-4159.1998.70031227.x.
To determine the transport and utilization of dietary saturated, monounsaturated, and n-6 and n-3 polyunsaturated fatty acids for the developing brain and other organs, artificially reared rat pups were fed a rat milk substitute containing the perdeuterated (each 97 atom% deuterium) fatty acids, i.e., palmitic, stearic, oleic, linoleic, and linolenic, from day 7 after birth to day 14 as previously described. Fatty acids in lipid extracts of the liver, lung, kidney, and brain were analyzed by gas chromatography-mass spectrometry to determine their content of each of the deuterated fatty acids. The uptake and metabolism of perdeuterated fatty acid lead to the appearance of three distinct groups of isotopomers: the intact perdeuterated, the newly synthesized (with recycled deuterium), and the natural unlabeled fatty acid. The quantification of these isotopomers permits the estimation of uptake and de novo synthesis of these fatty acids. Intact perdeuterated palmitic, stearic, and oleic acids from the diet were found in liver, lung, and kidney, but not in brain. By contrast, perdeuterated linoleic acid was found in all these organs. Isotopomers of fatty acid from de novo synthesis were observed in palmitic, oleic, and stearic acids in all tissues. The highest enrichment of isotopomers with recycled deuterium was found in the brain. The data indicate that, during the brain growth spurt and the prelude to myelination, the major saturated and monounsaturated fatty acids in brain lipids are exclusively produced locally by de novo biosynthesis. Consequently, the n-6 and n-3 polyunsaturated fatty acids must be transported and delivered to the brain by highly specific mechanisms.
为了确定膳食中饱和脂肪酸、单不饱和脂肪酸以及n-6和n-3多不饱和脂肪酸在发育中的大脑和其他器官中的转运及利用情况，如前所述，从出生后第7天至第14天，给人工饲养的新生大鼠幼崽喂食含有全氘代（每个脂肪酸中氘原子含量为97%）脂肪酸的大鼠代乳品，这些脂肪酸包括棕榈酸、硬脂酸、油酸、亚油酸和亚麻酸。通过气相色谱-质谱联用仪分析肝脏、肺、肾脏和大脑脂质提取物中的脂肪酸，以确定各氘代脂肪酸的含量。全氘代脂肪酸的摄取和代谢会产生三类不同的同位素异构体：完整的全氘代脂肪酸、新合成的（含循环利用的氘）脂肪酸以及天然未标记的脂肪酸。对这些同位素异构体进行定量分析，可以估算这些脂肪酸的摄取量和从头合成量。在肝脏、肺和肾脏中发现了来自饮食的完整全氘代棕榈酸、硬脂酸和油酸，但在大脑中未发现。相比之下，在所有这些器官中都发现了全氘代亚油酸。在所有组织的棕榈酸、油酸和硬脂酸中都观察到了从头合成的脂肪酸的同位素异构体。大脑中发现了循环利用氘的同位素异构体的最高富集量。数据表明，在大脑生长突增期和髓鞘形成前期，脑脂质中的主要饱和脂肪酸和单不饱和脂肪酸完全由局部从头生物合成产生。因此，n-6和n-3多不饱和脂肪酸必须通过高度特异性的机制转运并输送到大脑。
