檸檬酸攝取增進代謝與認知上的健康狀況

Abstract

檸檬酸在細胞的代謝裡扮演了重要的角色，並且廣泛地存在於日常許多食物之中。基於頻繁攝取到此重要代謝物的可能性，本篇研究透過於吃高脂飼料的實驗老鼠的飲水中添加檸檬酸來探討外加的檸檬酸對代謝與認知功能的影響。 在代謝方面，檸檬酸的攝取減少了食物造成的肥胖，使得身體脂肪重量較輕也減少了肝臟的脂肪堆積。較輕的體重同時也伴隨著較好維持體內葡萄糖恆定的能力與較低的血液中膽固醇濃度，顯示攝取檸檬酸的老鼠有較健康的代謝。在這些老鼠的肝臟細胞內，參與脂質新生與膽固醇合成代謝途徑的相關基因表現量也發現有被調降。此外，β-羥基丁酸(β-hydroxybutyrate，酮體的一種)在檸檬酸攝取老鼠血液中的濃度也比較高。 在認知功能方面，檸檬酸的攝取增進了老鼠的記憶行為表現，而未影響牠們的情緒狀態、運動能力與嗅覺功能。同時，海馬迴中位於齒狀迴(dentate gyrus)的顆粒細胞（granule cell）也有較高的樹突棘（dendritic spine）密度，它們的神經結構則未發生改變。 在研究的最後部分，我們改而直接將β-羥基丁酸加入實驗老鼠的飲水中，並發現記憶行為表現也因此而變好。此發現支持了檸檬酸可能是透過促進酮體的產生來增進記憶的可能性。 總括來說，本研究揭示了檸檬酸攝取對代謝與認知的健康益處，且提出了可能的背後機制。

Citrate plays a pivotal role in cellular metabolism and is contained in many of our daily foods. Due to the frequent acquisition of the critical metabolite, this study aims to investigate the effect of exogenous citrate on metabolism and cognitive function by administrating citrate in the drinking water of the experimental mice under high-fat diet condition. In metabolism, citrate consumption mitigated the diet-induced adiposity in the experimental mice, resulting in lower fat mass and lower lipid accumulation in the liver. In addition to reduced body weight, the mice also showed better ability to maintain glucose homeostasis and lower levels of circulating cholesterol, which implies an improved metabolic health. In the cellular level, genes involving in lipogenesis and cholesterol biosynthesis pathways were found to be downregulated in the liver of the mice. Besides, the circulating level of the ketone body, β-hydroxybutyrate, was significantly higher in the citrate consuming mice. In cognitive function, citrate consumption enhanced the memory performances of the mice without affecting the mood status, motor ability and olfactory function. Meanwhile, the dendritic spine density of the dentate gyrus granule cells in the hippocampus was increased while the neuronal structure was not altered. Finally, we directly administered β-hydroxybutyrate to the drinking water of mice and found memory performances to be enhanced, which provides an evidence that citrate may improve memory through induction of ketogenesis. In brief, this study sheds light on the beneficial effects of citrate consumption on metabolic and cognitive health, and proposes the possible underlying mechanism.