循環農業：農業廢棄物再資源化【食品暨應用生物科技學系/蔣恩沛特聘教授】
| 論文篇名 | 英文：Ketogenic Diet Consumption Inhibited Mitochondrial One Carbon Metabolism 中文：生酮飲食抑制線粒體之單碳代謝 |
| 期刊名稱 | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES |
| 發表年份,卷數,起迄頁數 | 2022, 23, 3650 |
| 作者 | Hsu, Fan-Yu; Liou, Jia-Ying; Tang, Feng-Yao; Sou, Nga-Lai; Peng, Jian-Hau; Chiang, En-Pei Isabel(蔣恩沛)* |
| DOI | 10.3390/ijms23073650 |
| 中文摘要 | 生酮飲食現今廣泛流行。因此其長期對個體代謝的影響值得更仔細深入地追蹤。線粒體衍生的甲酸在哺乳動物發育及單碳代謝具關鍵作用。甘氨酸裂解系統) 是線粒體衍生的單碳單位的另一重要來源。我們研究生酮狀態如何調節線粒體甲酸生成和單碳代謝的碳流分配。我們以生理劑量 (1 mM 與 10 mM) 的 β-羥基丁酸 (βHB) 處理的 HepG2 細胞用作體外生酮模型。以八周雄性 C57BL/6JNarl 小鼠接受中鏈富含脂肪酸的生酮飲食 (MCT-KD) 持續 8 週當作體內模式, 對照正常飲食小鼠進行研究, 並進行穩定同位素標記實驗。我們發現MCT-KD 對減肥和減脂有顯著效果。βHB 與 MCT-KD 的攝取顯著抑制線粒體甘氨酸裂解系統衍生甲酸合成脫氧胸苷 (dTMP)。與之一致得是, MCT-KD 抑制血漿甲酸濃度以及絲氨酸和甘氨酸合成的甲酸代謝流，同時降低線粒體衍生的甲酸在從絲氨酸合成甲硫胺酸中的部分供給。此為第一個發現生酮飲食抑制線粒體單碳代謝及甘氨酸裂解系統的研究。隨著世界各地生酮飲食的普及，人們長期進行生酮飲食時應該更加意識到其可能造成代謝紊亂。 |
| 英文摘要 | Given the popularity of ketogenic diets, their potential long-term consequences deserve to be more carefully monitored. Mitochondrially derived formate has a critical role in mammalian one-carbon (1C) metabolism and development. The glycine cleavage system (GCS) accounts for another substantial source for mitochondrially derived 1C units. Objective: We investigated how the ketogenic state modulates mitochondrial formate generation and partitioning of 1C metabolic fluxes. Design: HepG2 cells treated with physiological doses (1 mM and 10 mM) of β-hydroxybutyrate (βHB) were utilized as the in vitro ketogenic model. Eight-week male C57BL/6JNarl mice received either a medium-chain fatty-acid-enriched ketogenic diet (MCT-KD) or a control diet AIN 93M for 8 weeks. Stable isotopic labeling experiments were conducted. Results and Conclusions: MCT-KD is effective in weight and fat loss. Deoxythymidine (dTMP) synthesis from the mitochondrial GCS-derived formate was significantly suppressed by βHB and consumption of MCT-KD. Consistently, plasma formate concentrations, as well as the metabolic fluxes from serine and glycine, were suppressed by MCT-KD. MCT-KD also decreased the fractional contribution of mitochondrially derived formate in methionine synthesis from serine. With the worldwide application, people and medical professionals should be more aware of the potential metabolic perturbations when practicing a long-term ketogenic diet. |
| 發表成果與本中心研究主題相關性 | 建立質譜代謝路徑追蹤平台之應用 (說明: 本研究建立代謝流追蹤平台發現生酮飲食抑制線粒體單碳代謝及甘氨酸裂解系統, 人們長期進行生酮飲食時應該更加意識到其可能造成代謝紊亂。本研究所建立的系統和方法目前已經應用在永續及智慧農業領域) |
