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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
| dc.contributor.author | Yu-Shiuan Lin | en |
| dc.contributor.author | 林雨萱 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:17:34Z | - |
| dc.date.available | 2025-08-31 | |
| dc.date.copyright | 2020-09-23 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-31 | |
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(2016). Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease. Nature Communications, 7(1), 13082. doi:10.1038/ncomms13082 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78762 | - |
| dc.description.abstract | 飲食深深的影響生物體的代謝平衡，而代謝平衡調節許多生理功能且與許多疾病成因有關，然而至今飲食如何調節生物的生理反應仍有待釐清，本研究利用秀麗桿線蟲作為模式生物去剖析飲食所致的代謝分子機制，其中包括脂質磷脂醯膽鹼(Phosphatidylcholine)的含量以及鞘脂(sphingolipid)穩定平衡的影響，另外，利用高通量核糖核酸測序(RNA-seq)分析線蟲在飲食影響下基因表現的調控，而發現一個調控鞘脂代謝基因具有飲食差異性的基因表現，因此我們創造此基因轉殖的線蟲去探討其對於飲食的反應，經過實驗測試後我們發現許多的轉錄因子參與這個基因的表現，其中特別是胰島素訊號路徑扮演一個重要的角色，他可能是透過調節DAF-16 入核去影響的基因表現，進而調控脂肪含量。再者，本研究發現該基因可以自我調節基因表現，其原因是透過影響磷脂醯膽鹼和鞘脂質相關代謝物而正回饋自己的基因表現，且其回饋反應可能是透過胰島素受體訊號路徑，簡而言之，飲食可以透過調節基因的表現去影響生物的代謝平衡，其代謝物又能影響飲食所調節的生理機制。 | zh_TW |
| dc.description.abstract | Diets profoundly influence organismal metabolism homeostasis, which affect numerous physiological processes and associate with various diseases. To date, how the diets regulate host physiological responses still remain elucidated. Here, we utilize Caenorhabditis elegans as a model organism to dissect the underlying molecular mechanisms about how diets impact on organismal metabolism homeostasis, including PC level and sphingolipid metabolism to affect lipid content. By analysis of RNA-seq data, we found a gene involved in sphingolipid metabolism is differentially expressed and generated transgenic worms to determine its impact on diets-mediated responses. After examination, we found several transcription factors participate in the regulation of this gene expression in response to different diets. Specifically, DAF-2/IIS signaling pathway plays an important role via inhibiting the nuclear localization of the Foxo transcription factor DAF-16 to regulate this gene expression and further affect lipid content level in animals. Moreover, we found that this gene could self-regulate its expression, possibly by feedback to DAF-2/IIS signaling. Altogether, diets could regulate organismal genes expression to influence host metabolism homeostasis and these metabolites alterations also contribute to diets-mediated responses. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:17:34Z (GMT). No. of bitstreams: 1 U0001-1908202022221200.pdf: 4283438 bytes, checksum: 3403e2c63828a3aa8bdd7ae2cd7cf57d (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 誌謝 i 中文摘要 iii Abstract iv Introduction 1 Diet has great impact on physiology in organisms. 1 Phosphatidylcholine (PC) 2 Acid sphingomyelinase (ASMase, ASM, SMPD1) 3 DAF-16/FOXO and Insulin/insulin-like growth factor (IGF) signaling (IIS) pathway 6 Autophagy 9 C. elegans is the powerful model to investigate the diet-mediated regulations 13 Material and method 14 Caenorhabditis elegans strains and culture 14 Caenorhabditis elegans synchronization 16 Oil-Red-O (ORO) staining 16 Western blotting 17 Construction and microinjection 18 fos-1 double-stranded RNA processing and microinjection 18 Microscopy visualization 19 Result 20 DA1877 promotes the transcriptional expression of asm-3 involved in PC synthesis pathway 20 Transcription factor daf-16 functions as a repressor of asm-3 on DA1877 diet via its nuclear translocation regulation 21 DA1877-mediated upregulation of asm-3 requires IIS pathway 23 ins-7 functions in DAF-16/IIS signaling pathway to regulate DA1877-mediated asm-3 expression 25 PC homeostasis influences asm-3 expression on DA1877 diet 26 asm-3 contributes to DA1877-mediated lipid reduction 27 Discussion 29 C. elegans ASM-3 may be secreted and its C-terminus is not cleaved 29 asm-3 did not function in DA1877-diet induced neuroplasticity 30 DA1877 dominantly results in autophagosome-lysosome fusion defect not via asm-3 or affecting PC synthesis 31 Figures 33 Figure 1. DA1877-fed worms show higher PC level and higher asm-3 expression level. 34 Figure 2. The transcription factors of asm-3 play the different roles in diet-mediated asm-3 regulation. 41 Figure 3. DA1877 diet regulated asm-3 expression via IIS pathway and influence DAF-16 nuclear translocation. 45 Figure 4. ins-7 and daf-16 play the similar roles in the regulation of asm-3 expression in DA1877 diet 48 Figure 5. PC-associated metabolites influence expression of asm-3 in DA1877 diet. 50 Figure 6. asm-3 and pcyt-1 are in the same pathway to affect lipid content in DA1877 diet. 53 Figure 7. Model 54 Supplemantary figures 55 Figure 1S. The location of ASM-3 in C. elegans and its structure analysis. 57 Figure 2S. asm-3 had no effect on diet-specific aldicarb responsive. 59 Figure 3S. asm-3 mutant block autophagosome-lysosome fusion om DA1877 diet. 63 Figure 4S. klu-1 and fos-1, transcription factors of asm-3, were not major regulator in diet-specific effect. 66 Tables 68 Table 1. Downstream genes of DAF-2/DAF-16 pathway had significantly differential expression level on different diet by RNA-seq analysis. 70 Table 2. the expression of ins-7 is the highest in all insulin genes by RNA-seq analysis. 71 Supplementary: One-way ANOVA analysis 72 Supplementary: Two-way ANOVA analysis 75 Reference 94 | |
| dc.language.iso | en | |
| dc.subject | 鞘脂 | zh_TW |
| dc.subject | 秀麗隱桿線蟲 | zh_TW |
| dc.subject | 飲食 | zh_TW |
| dc.subject | 代謝 | zh_TW |
| dc.subject | 脂質 | zh_TW |
| dc.subject | 脂肪 | zh_TW |
| dc.subject | Caenorhabditis elegans | en |
| dc.subject | lipid | en |
| dc.subject | diet | en |
| dc.subject | fat | en |
| dc.subject | sphingolipid | en |
| dc.subject | metabolism | en |
| dc.title | 在線蟲內飲食調控酸性鞘磷脂酶 | zh_TW |
| dc.title | Regulation of acid sphingomyelinase by bacterial dietary effect in C. elegans | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳昌熙(Chang-Shi Chen),廖秀娟(Hsiu-Chuan Liao) | |
| dc.subject.keyword | 秀麗隱桿線蟲,鞘脂,脂肪,脂質,代謝,飲食, | zh_TW |
| dc.subject.keyword | Caenorhabditis elegans,sphingolipid,fat,lipid,metabolism,diet, | en |
| dc.relation.page | 102 | |
| dc.identifier.doi | 10.6342/NTU202004108 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-08-31 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-08-31 | - |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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