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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群 | zh_TW |
| dc.contributor.author | 王儷瑗 | zh_TW |
| dc.contributor.author | Li-Yuan Wang | en |
| dc.date.accessioned | 2021-07-11T15:01:42Z | - |
| dc.date.available | 2024-08-19 | - |
| dc.date.copyright | 2019-08-26 | - |
| dc.date.issued | 2019 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | 1. Folick, A., Oakley, H.D., Yu, Y., Armstrong, E.H., Kumari, M., Sanor, L., Moore, D.D., Ortlund, E.A., Zechner, R., and Wang, M.C. (2015). Lysosomal signaling molecules regulate longevity in <em>Caenorhabditis elegans</em>. Science 347, 83-86.
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Xu, N., Zhang, S.O., Cole, R.A., McKinney, S.A., Guo, F., Haas, J.T., Bobba, S., Farese, R.V., Jr., and Mak, H.Y. (2012). The FATP1-DGAT2 complex facilitates lipid droplet expansion at the ER-lipid droplet interface. J Cell Biol 198, 895-911. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78520 | - |
| dc.description.abstract | 脂肪對於大部分的生物體是必要存在的物質，它不止提供生存所需能量還是一個重要的調控因子。在脂肪分解的過程中，脂肪酸會被游離出來變成游離脂肪酸 (Free fatty acids)，而游離脂肪酸和其衍生物已被知道可當作訊號因子去調控基因轉錄啟動與酵素活化。但對於飲食影響而產生的脂肪訊號因子如何去影響生物體功能，我們所知卻還是很少。我們實驗室以線蟲 (C. elegans)當作模式生物並餵食不同的細菌來研究飲食對於生物體的影響。在我們實驗室過去的研究中，發現線蟲在餵食不同飲食的狀況下，線蟲的生物體表現在脂肪含量和移動性相當不一樣。為了剖析差異中的分子機轉，我們使用了氣相層析質譜儀 (GC-MS)和液相層析質譜 (LC-MS)來分析線蟲和所食用的細菌。另外我們也採用阻斷線蟲產生這些游離脂肪酸以及外加游離脂肪酸的方法來探討其在線蟲中的功能。我們發現在特定的飲食餵食下特別的長碳鏈脂肪酸會影響線蟲內酸性胞器數目。另外也發現在特定飲食餵食下的突變線蟲可以回復神經傳遞物質的活性以及身體大小。而有些參與在脂肪代謝的酵素在不同飲食下基因轉錄表現也不同，其顯示飲食可能透過基因轉錄來調控線蟲脂肪組成和生理現象。總結來說，我們的實驗結果呈現了飲食上的差異會影響生物體脂質組成進而產生不同的脂質訊號分子並改變生物體的生理變化。 | zh_TW |
| dc.description.abstract | Lipids are important for cellular and physiological functions. Emerging evidences show that lipids not only provide energy but also play regulatory and signaling roles in multiple cellular processes. During lipid breakdown, the released free fatty acids (FFA) or resultant lipid derivatives have been shown to function as signaling molecules to regulate gene transcriptional activation and as co-activators to control enzyme activities. Still, little is known about how diets may be involved in lipid signaling to regulate host physiology. In our lab, we used C. elegans as a modal organism and fed them on different diets to study the dietary effects on C. elegans physiology. Our previous data indicated that C. elegans on different diets showed several physiological changes, including lipid content and locomotion. To dissect the mechanisms, we performed lipodomic analyses using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) approaches to identify variations in lipid compositions among bacteria and C. elegans fed on them. In addition, we examined the effects of the lipid compositions in bacteria and C. elegans may impact on C. elegans phenotypic changes by genetic mutations and lipid supplementation experiments. We found specific PUFAs that control the intestinal acidic organelles numbers of C. elegans fed on one but not the other bacterial diets. In addition, we found that some bacterial diet can rescue the phenotypes of uncoordinated movement and small body size in a mutant defective in lipid metabolism. Moreover, we found some genes involved in lipid metabolism are differentially expressed in worms fed on different diets, indicating that diets may modulate lipid composition and physiology through transcriptional regulation of these genes. Together, our results revealed that diets could impact lipidome within the organism, modulating lipid signaling molecules which may result in alteration in lifespan, locomotion, lipid contents etc. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:01:42Z (GMT). No. of bitstreams: 1 ntu-108-R06b43030-1.pdf: 1832566 bytes, checksum: 18bb21d5b6dbec7cc86612022c1f6f1a (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii Introduction 1 Dietary effects on human health 1 Lipid and cell signaling 2 Lipidomic analysis 4 Lipases and lipid-binding proteins 6 Materials and Methods 9 C. elegans strains 9 Bacterial strains and plates preparation 9 Bacteria Mixture Assay 10 C. elegans synchronization 10 GFP reporter analysis and quantification 11 Oil Red O staining and quantification 11 Lipid extraction of worms 12 Lipid extraction of bacteria 13 Gas Chromatography Analysis for Fatty Acid Profiling 14 Liquid Chromatography Analysis for Fatty Acid Profiling 15 Aldicarb Sensitivity Assay 15 LysoTracker staining 16 Locomotion assay 17 Results 18 Comamonas DA1877 diet contains bioactive molecules to exhibit dominant effect on lipid content and locomotion in the worms 18 Comamonas DA1877 is enriched in palmitoleic acid (16:1n7) compared to E.coli OP50 19 FA 16:1n7, FA 18:1, and FA 18:4n3 appeared accumulation in DA1877-fed worms 19 DA1877-fed worms showed less cyclopropane fatty acid 22 fat-1 participates in the lipid content reduction in DA1877-fed worms 23 DA1877-mediated LRO density increase could be suppressed by fat-1 24 fat-3 is required for aldicarb sensitivity and lipid content on OP50 diets 26 DA1877 diet induced several lysosomal lipases and lipid binding proteins significantly at transcriptional level 27 Enhanced free fatty acids signal in DA1877 worms were not through specific lysosomal lipase 29 Lysosomal lipase could modulate lipid metabolism and neural activity on both diets 30 Discussion 31 The reduction expression of fat-5 and fat-7 in DA1877-fed worms 31 The dominant effect of DA1877 on neurotransmission enhancement by aldicarb sensitivity 32 Lysosomal lipase activity and LROs 33 EPA signal effect on DA1877 diet 34 Figures 36 Figure 1. DA1877 diets exhibited the dominant effect on worm lipid content and locomotion 36 Figure 2. Comamonas DA1877 is enriched in palmitoleic acid (16:1n7) and absent of cyclopropane fatty acid 39 Figure 3. Free fatty acid C16:1, C18:1 and C18:4 are increased in DA-fed worms 41 Figure 4. C. elegans fatty acid synthesis pathway with relative transcriptional expression of elongases and desaturases on different diets 43 Figure 5. DA1877-mediated lipid content increase in fat-1 mutants could be rescued by PUFA 45 Figure 6. Loss of fat-1 reversed the high levels of LysoTracker signals in DA1877-fed worms and could be rescued by EPA (20:5n3) 48 Figure 7. Loss of fat-3 exhibits different effects on aldicarb sensitivity and lipid content 50 Figure 8. DA1877 diet induced several lysosomal lipases and lipid binding proteins significantly at transcriptional level 53 Figure 9. Increased free fatty acids in DA1877 worms were not via specific lysosomal lipase, but monounsaturated fatty (18:1) and EPA (20:5n3) could be regulated by glo-1 56 Figure 10. lipl-1, lipl-2 and lipl-5 could modulate lipid metabolism and neural activity on both diets 60 Supplementary 62 Figure S1. genetic mutation disrupted PC synthesis and ceramide de novo pathway suppressed neural transmission enhancement in DA1877-fed worms 63 Figure S2. LC-MS analysis of lysosomal lipase mutants and LRO mutants 68 Table S1. (Figure 5A) 70 Table S2. (Figure 5A) 71 Table S3. (Figure 5B) 72 Table S4. (Figure 5C) 73 Table S5. (Figure 7C) 74 Table S6. (Figure 6B) 75 Table S7. (Figure 6B) 76 Table S8. (Figure 10A) 77 Table S9. (Figure 10B) 77 Table S10. (Figure S1B) 78 Table S11. (Figure S1D) 79 Acknowledgements 81 Reference 82 | - |
| dc.language.iso | en | - |
| dc.subject | 游離脂肪酸 | zh_TW |
| dc.subject | 酸性胞器 | zh_TW |
| dc.subject | 脂質組成 | zh_TW |
| dc.subject | 秀麗隱桿線蟲 | zh_TW |
| dc.subject | 運動性 | zh_TW |
| dc.subject | Free fatty acid | en |
| dc.subject | C. elegans | en |
| dc.subject | lipid composition | en |
| dc.subject | acidic organelles | en |
| dc.subject | movement | en |
| dc.title | 透過特定脂肪訊號調控線蟲脂肪代謝及神經活性 | zh_TW |
| dc.title | Diets regulate fat levels and neural activity through specific lipid signaling | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 107-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 陳昌熙;王昭雯;金翠庭 | zh_TW |
| dc.contributor.oralexamcommittee | ;; | en |
| dc.subject.keyword | 秀麗隱桿線蟲,游離脂肪酸,脂質組成,酸性胞器,運動性, | zh_TW |
| dc.subject.keyword | C. elegans,Free fatty acid,lipid composition,acidic organelles,movement, | en |
| dc.relation.page | 92 | - |
| dc.identifier.doi | 10.6342/NTU201904046 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2019-08-19 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | - |
| dc.date.embargo-lift | 2024-08-26 | - |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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