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Cardiac tissue citric acid cycle intermediates in exercised very long‐chain acyl‐CoA dehydrogenase‐deficient mice fed triheptanoin or medium‐chain triglyceride
Journal of Inherited Metabolic Disease ( IF 4.2 ) Pub Date : 2020-07-10 , DOI: 10.1002/jimd.12284 Garen Gaston 1 , Jon A Gangoiti 2 , Shelley Winn 1 , Benjamin Chan 3 , Bruce A Barshop 2 , Cary O Harding 1 , Melanie B Gillingham 1
Journal of Inherited Metabolic Disease ( IF 4.2 ) Pub Date : 2020-07-10 , DOI: 10.1002/jimd.12284 Garen Gaston 1 , Jon A Gangoiti 2 , Shelley Winn 1 , Benjamin Chan 3 , Bruce A Barshop 2 , Cary O Harding 1 , Melanie B Gillingham 1
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Anaplerotic odd‐chain fatty acid supplementation has been suggested as an approach to replenish citric acid cycle intermediate (CACi) pools and facilitate adenosine triphosphate (ATP) production in subjects with long‐chain fatty acid oxidation disorders, but the evidence that cellular CACi depletion exists and that repletion occurs following anaplerotic substrate supplementation is limited. We exercised very long‐chain acyl‐CoA dehydrogenase‐deficient (VLCAD−/−) and wild‐type (WT) mice to exhaustion and collected cardiac tissue for measurement of CACi by targeted metabolomics. In a second experimental group, VLCAD−/− and WT mice that had been fed chow prepared with either medium‐chain triglyceride (MCT) oil or triheptanoin for 4 weeks were exercised for 60 minutes. VLCAD−/− mice exhibited lower succinate in cardiac muscle at exhaustion than WT mice suggesting lower CACi in VLCAD−/− with prolonged exercise. In mice fed either MCT or triheptanoin, succinate and malate were greater in VLCAD−/− mice fed triheptanoin compared to VLCAD−/− animals fed MCT but lower than WT mice fed triheptanoin. Long‐chain odd acylcarnitines such as C19 were elevated in VLCAD−/− and WT mice fed triheptanoin suggesting some elongation of the heptanoate, but it is unknown what proportion of heptanoate was oxidized vs elongated. Prolonged exercise was associated with decreased cardiac muscle succinate in VLCAD−/− mice in comparison to WT mice. VLCAD−/− fed triheptanoin had increased succinate compared to VLCAD−/− mice fed MCT but lower than WT mice fed triheptanoin. Cardiac CACi were higher following dietary ingestion of an anaplerotic substrate, triheptanoin, in comparison to MCT.
中文翻译：
喂食三庚酸甘油酯或中链甘油三酯的极长链酰基辅酶A脱氢酶缺陷小鼠的心脏组织柠檬酸循环中间体
已建议补充奇数链脂肪酸补充剂作为补充柠檬酸循环中间体 (CACi) 池和促进长链脂肪酸氧化障碍受试者三磷酸腺苷 (ATP) 产生的一种方法，但存在细胞 CACi 耗竭的证据并且在补补底物补充后发生的补充是有限的。我们使极长链酰基辅酶A脱氢酶缺陷（VLCAD-/-）和野生型（WT）小鼠精疲力竭，并收集心脏组织以通过靶向代谢组学测量CACi。在第二个实验组中，已喂食用中链甘油三酯 (MCT) 油或三庚酸甘油酯制备的食物 4 周的 VLCAD-/- 和 WT 小鼠运动 60 分钟。VLCAD-/- 小鼠在衰竭时的心肌中琥珀酸含量低于 WT 小鼠，表明 VLCAD-/- 长期运动时 CACi 较低。在喂食 MCT 或三庚酸甘油酯的小鼠中，与喂食 MCT 的 VLCAD-/- 小鼠相比，喂食三庚酸的 VLCAD-/- 小鼠的琥珀酸和苹果酸更高，但低于喂食三庚酸的 WT 小鼠。长链奇数酰基肉碱（如 C19）在 VLCAD-/- 和喂食三庚酸甘油酯的 WT 小鼠中升高，表明庚酸有一定程度的延伸，但尚不清楚庚酸被氧化与被拉长的比例。与 WT 小鼠相比，长时间运动与 VLCAD-/- 小鼠心肌琥珀酸减少有关。与喂食 MCT 的 VLCAD-/- 小鼠相比，喂食 VLCAD-/- 的三庚酸甘油酯的琥珀酸增加，但低于喂食三庚酸甘油酯的 WT 小鼠。
更新日期：2020-07-10
中文翻译：
喂食三庚酸甘油酯或中链甘油三酯的极长链酰基辅酶A脱氢酶缺陷小鼠的心脏组织柠檬酸循环中间体
已建议补充奇数链脂肪酸补充剂作为补充柠檬酸循环中间体 (CACi) 池和促进长链脂肪酸氧化障碍受试者三磷酸腺苷 (ATP) 产生的一种方法，但存在细胞 CACi 耗竭的证据并且在补补底物补充后发生的补充是有限的。我们使极长链酰基辅酶A脱氢酶缺陷（VLCAD-/-）和野生型（WT）小鼠精疲力竭，并收集心脏组织以通过靶向代谢组学测量CACi。在第二个实验组中，已喂食用中链甘油三酯 (MCT) 油或三庚酸甘油酯制备的食物 4 周的 VLCAD-/- 和 WT 小鼠运动 60 分钟。VLCAD-/- 小鼠在衰竭时的心肌中琥珀酸含量低于 WT 小鼠，表明 VLCAD-/- 长期运动时 CACi 较低。在喂食 MCT 或三庚酸甘油酯的小鼠中，与喂食 MCT 的 VLCAD-/- 小鼠相比，喂食三庚酸的 VLCAD-/- 小鼠的琥珀酸和苹果酸更高，但低于喂食三庚酸的 WT 小鼠。长链奇数酰基肉碱（如 C19）在 VLCAD-/- 和喂食三庚酸甘油酯的 WT 小鼠中升高，表明庚酸有一定程度的延伸，但尚不清楚庚酸被氧化与被拉长的比例。与 WT 小鼠相比，长时间运动与 VLCAD-/- 小鼠心肌琥珀酸减少有关。与喂食 MCT 的 VLCAD-/- 小鼠相比，喂食 VLCAD-/- 的三庚酸甘油酯的琥珀酸增加，但低于喂食三庚酸甘油酯的 WT 小鼠。
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