Brain Physiology and Metabolism Section, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
J Lipid Res. 2010 Oct;51(10):2940-6. doi: 10.1194/jlr.M005595. Epub 2010 Jul 9.
Isotope feeding studies report a wide range of conversion fractions of dietary shorter-chain polyunsaturated fatty acids (PUFAs) to long-chain PUFAs, which limits assessing nutritional requirements and organ effects of arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-3) acids. In this study, whole-body (largely liver) steady-state conversion coefficients and rates of circulating unesterified linoleic acid (LA, 18:2n-6) to esterified AA and other elongated n-6 PUFAs were quantified directly using operational equations, in unanesthetized adult rats on a high-DHA but AA-free diet, using 2 h of intravenous [U-(13)C]LA infusion. Unesterified LA was converted to esterified LA in plasma at a greater rate than to esterified gamma-linolenic (gamma-LNA, 18:3n-6), eicosatrienoic acid (ETA, 20:3n-6), or AA. The steady-state whole-body synthesis-secretion (conversion) coefficient k*(i) to AA equaled 5.4 x 10(-3) min(-1), while the conversion rate (coefficient x concentration) equaled 16.1 micromol/day. This rate exceeds the reported brain AA consumption rate by 27-fold. As brain and heart cannot synthesize significant AA from circulating LA, liver synthesis is necessary to maintain their homeostatic AA concentrations in the absence of dietary AA. The heavy-isotope intravenous infusion method could be used to quantify steady-state liver synthesis-secretion of AA from LA under different conditions in rodents and in humans.
同位素喂养研究报告表明，膳食中较短链多不饱和脂肪酸（PUFAs）转化成长链 PUFAs 的转化率差异很大，这限制了评估花生四烯酸（AA，20:4n-6）和二十二碳六烯酸（DHA，22:6n-3）酸的营养需求和器官效应。在这项研究中，使用操作方程直接量化了高脂肪但不含 AA 的饮食喂养的成年大鼠在清醒状态下全身（主要是肝脏）稳态转化系数和循环游离亚油酸（LA，18:2n-6）转化为酯化 AA 和其他伸长 n-6 PUFAs 的速率，使用 2 小时静脉内[U-(13)C]LA 输注。游离 LA 在血浆中转化为酯化 LA 的速度大于转化为酯化 γ-亚麻酸（γ-LNA，18:3n-6）、二十碳三烯酸（ETA，20:3n-6）或 AA。全身稳态合成-分泌（转化）系数 k*(i) 到 AA 等于 5.4 x 10(-3) min(-1)，而转化率（系数 x 浓度）等于 16.1 微摩尔/天。这一速率超过了报告的大脑 AA 消耗速率的 27 倍。由于大脑和心脏不能从循环 LA 合成大量 AA，因此在没有膳食 AA 的情况下，肝脏合成是维持其稳态 AA 浓度所必需的。这种重同位素静脉内输注方法可用于在不同条件下定量啮齿动物和人类肝脏从 LA 合成-分泌 AA 的稳态。
