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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 腦與心智科學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66171
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dc.contributor.advisor王培育(Pei-Yu Wang)
dc.contributor.authorCheng-Sheng Linen
dc.contributor.author林承聖zh_TW
dc.date.accessioned2021-06-17T00:24:20Z-
dc.date.available2025-03-13
dc.date.copyright2020-03-13
dc.date.issued2020
dc.date.submitted2020-02-11
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66171-
dc.description.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。
zh_TW
dc.description.abstractCitrate 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.
en
dc.description.provenanceMade available in DSpace on 2021-06-17T00:24:20Z (GMT). No. of bitstreams: 1
ntu-109-R05454012-1.pdf: 4906145 bytes, checksum: 7578cb17eb7e64cd6305798b3649d650 (MD5)
Previous issue date: 2020
en
dc.description.tableofcontents口試委員會審定書 i
誌謝 ii
中文摘要 iv
Abstract v
Graphical Abstract vi
Abbreviations vii
Contents viii
Chapter 1 Introduction 1
1.1 Citrate as a central metabolite and regulator of cellular metabolism 1
1.2 Lipid synthesis and abnormal lipid accumulation in liver 1
1.3 Ketogenesis and the link to memory enhancement 2
1.4 Aim 3
Chapter 2 Materials and Methods 5
2.1 Animals 5
2.2 Metabolic monitoring 6
2.3 Glucose and insulin tolerance tests 6
2.4 Body composition measurement 7
2.5 Biochemical analyses 7
2.5.1 High performance liquid chromatography (HPLC) 7
2.5.2 Tissue triglyceride and total cholesterol contents assaying 8
2.5.3 Serum biochemical analysis 8
2.5.4 Ketone body measurement 9
2.6 RNA extraction and quantitative real-time PCR 9
2.7 Behavior tests 10
2.7.1 Elevated plus maze 10
2.7.2 Open field test 10
2.7.3 Novel object recognition test 10
2.7.4 Three-chamber social test 11
2.7.5 Rotarod test 12
2.7.6 Tail suspension test 12
2.7.7 Forced swim test 12
2.7.8 Buried food test 12
2.8 Morphological analysis 13
2.8.1 Golgi-Cox impregnation 13
2.8.2 Dendritic structure and spine density analyses 13
2.9 Oil red O staining 14
2.10 Statistical analysis 15
Chapter 3 Results 16
3.1 Citrate administration in water increased circulating citrate level 16
3.2 Reduced body weight in high-citrate consuming mice 16
3.3 High citrate level moderately affected the metabolism of mice 17
3.4 High-citrate consuming improved metabolic health 17
3.5 High-citrate consumption ameliorated lipid metabolism 18
3.6 Citrate administration upregulated ketogenesis 19
3.7 Better memory performances of the citrate-consuming mice 20
3.8 Chronic ingestion of citrate did not alter mood status, motor performance and olfactory function 20
3.9 Citrate administration increased spine density without altering the neuronal structure of DG granule cells 21
3.10 Direct administration of β-hydroxybutyrate enhanced memory performances 21
Chapter 4 Discussion 23
Chapter 5 Table and Figures 27
Chapter 6 References 44
dc.language.isoen
dc.title檸檬酸攝取增進代謝與認知上的健康狀況zh_TW
dc.titleCitrate administration improves metabolic and cognitive healthen
dc.typeThesis
dc.date.schoolyear108-1
dc.description.degree碩士
dc.contributor.oralexamcommittee范守仁(Shou-Zen Fan),李立仁(Li-Jen Lee)
dc.subject.keyword檸檬酸,代謝,記憶,酮體,zh_TW
dc.subject.keywordCitrate,metabolism,memory,ketone body,en
dc.relation.page47
dc.identifier.doi10.6342/NTU202000400
dc.rights.note有償授權
dc.date.accepted2020-02-11
dc.contributor.author-college醫學院zh_TW
dc.contributor.author-dept腦與心智科學研究所zh_TW
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