Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor
Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor
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DOI：
10.1152/ajpregu.90795.2008
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发表时间：
2009-02-01
影响因子：
2.8
通讯作者：
Henry, Pierre-Gilles
中科院分区：
文献类型：
--
作者：
Andrews, Matthew T.;Russeth, Kevin P.;Henry, Pierre-Gilles
安德鲁斯 MT、拉塞斯 KP、德鲁斯 LR、亨利 P-G。适应性机制调节冬眠哺乳动物在从麻木中苏醒期间心脏和大脑中酮的优先利用。 Am J Physiol Regul Integr Comp Physiol 296：R383-R393，2009。首次发表于 2008 年 12 月 3 日； doi: 10.1152/ajpregu.90795.2008.-冬眠哺乳动物利用新陈代谢降低、体温过低和储存的脂肪在不进食的情况下存活长达 5 或 6 个月。我们发现十三线地松鼠（Spermophilus tridecemlineatus）的脂肪衍生酮 D-β-羟基丁酸（BHB）的血清水平在深度休眠期间最高，并且在整个冬眠季节与葡萄糖存在相互关系。当动物进入冬眠时，酮转运蛋白单羧酸转运蛋白 1 (MCT1) 在血脑屏障上表达上调。在 7 至 38℃ 的几种不同体温下，通过高分辨率 NMR 测量了大脑和心脏中 C-13 标记的 BHB 和葡萄糖的摄取和代谢。我们表明，BHB 和葡萄糖在体温和心率降低的条件下进入心脏和大脑，但它们作为燃料的利用具有高度选择性。在从麻木中醒来时，葡萄糖在很宽的体温范围内进入大脑，但新陈代谢很少，因为只检测到低水平的标记代谢物。这与 BHB 形成鲜明对比，BHB 不仅进入大脑，而且还通过三羧酸 (TCA) 循环进行代谢。心脏中也出现类似的情况，因为葡萄糖和 BHB 都被转运到器官中，但只有 BHB 中的 C-13 进入 TCA 循环。这一发现表明，燃料选择是在个体代谢途径水平上控制的，并且季节性诱导的适应机制导致冬眠期间 BHB 的战略利用。
Andrews MT, Russeth KP, Drewes LR, Henry P-G. Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor. Am J Physiol Regul Integr Comp Physiol 296: R383-R393, 2009. First published December 3, 2008; doi: 10.1152/ajpregu.90795.2008.-Hibernating mammals use reduced metabolism, hypothermia, and stored fat to survive up to 5 or 6 mo without feeding. We found serum levels of the fat-derived ketone, D-beta-hydroxybutyrate (BHB), are highest during deep torpor and exist in a reciprocal relationship with glucose throughout the hibernation season in the thirteen-lined ground squirrel (Spermophilus tridecemlineatus). Ketone transporter monocarboxylic acid transporter 1 (MCT1) is upregulated at the blood-brain barrier, as animals enter hibernation. Uptake and metabolism of C-13-labeled BHB and glucose were measured by high-resolution NMR in both brain and heart at several different body temperatures ranging from 7 to 38 C. We show that BHB and glucose enter the heart and brain under conditions of depressed body temperature and heart rate but that their utilization as a fuel is highly selective. During arousal from torpor, glucose enters the brain over a wide range of body temperatures, but metabolism is minimal, as only low levels of labeled metabolites are detected. This is in contrast to BHB, which not only enters the brain but is also metabolized via the tricarboxylic acid (TCA) cycle. A similar situation is seen in the heart as both glucose and BHB are transported into the organ, but only C-13 from BHB enters the TCA cycle. This finding suggests that fuel selection is controlled at the level of individual metabolic pathways and that seasonally induced adaptive mechanisms give rise to the strategic utilization of BHB during hibernation.