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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
| dc.contributor.author | Yi-Shan Li | en |
| dc.contributor.author | 李依珊 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:18:19Z | - |
| dc.date.available | 2025-08-19 | |
| dc.date.copyright | 2020-09-23 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-30 | |
| dc.identifier.citation | Al-Rashed, F., Ahmad, Z., Thomas, R., Melhem, M., Snider, A. J., Obeid, L. M., . . . Ahmad, R. (2020). Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α. bioRxiv, 2020.2005.2006.080382. doi:10.1101/2020.05.06.080382
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78773 | - |
| dc.description.abstract | 飲食調控生物體內的代謝並且影響其生理現象。不正常的飲食與代謝異常息息相關，如可能誘導細胞產生壓力，造成肥胖、糖尿病以及心血管疾病等代謝相關疾病。然而，飲食如何調控代謝並且引發細胞內壓力以及其防禦機制仍尚未明確。在先前實驗中我們證明了餵食不同細菌食物，會造成線蟲脂質含量改變及內質網壓力。而藉由分析脂肪染色及伴隨蛋白hsp-4螢光表現，我們發現了不同的細菌食物可能會藉由調控線蟲體內的磷脂膽鹼及鞘脂代謝途徑來降低脂質含量並誘導內質網壓力。我們證明了飲食造成的內質網壓力需要透過三種典型路徑來活化，並且可能會受脂質不平衡或是蛋白質平衡異常所影響。此外，我們的RNA定序分析結果，表明了不同飲食會影響免疫相關基因表現，而我們透過病原菌感染實驗來觀察線蟲存活率，發現了不同的飲食可以改變線蟲對外來病菌的防禦力。綜合上述結果，本研究證明了細菌食物與宿主間對於宿主的脂質代謝、內質網壓力以及免疫反應等系統性的代謝調控。 | zh_TW |
| dc.description.abstract | Diets provide nutrients and energy to regulate cellular metabolisms and influence physiological processes in organisms. Imbalanced diets are associated with metabolic disturbance. For example, lipid disequilibrium caused by imbalanced diets can induce intracellular stress and cause numerous metabolic disorders, including obesity, diabetes and cardiovascular diseases. Nevertheless, how diets modulate cellular metabolism, and trigger cellular stress and defense mechanisms remain elucidated. My former lab members found that different bacterial diets cause lipid composition alteration and induce ER stress in C. elegans when assayed using ORO staining and hsp-4p::gfp reporter, respectively. Here, my work shows that different bacterial diets cause lipid composition alteration and induce ER stress response in C. elegans through modulating host PC and sphingolipid metabolism. My work demonstrates that the diet-mediated ER stress requires three canonical signaling pathways and can be induced through lipid disequilibrium or disturbed proteostasis. Furthermore, using the RNA-sequencing analysis of C. elegans fed different bacterial diets and the pathogen infection assays, my work showed that bacterial diets regulate innate immunity by, at least in part, controlling the defense gene transcription. Taken together, my work shows that bacterial diets regulate host lipid metabolism, ER stress and immune response as systemic metabolic alteration. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:18:19Z (GMT). No. of bitstreams: 1 U0001-1908202022011800.pdf: 4482495 bytes, checksum: fe5ac77a9c5547aae38829c3095340b7 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 致謝 i
摘要 ii Abstract iii Introduction - 1 - Diets and the health - 1 - Lipid metabolism - 2 - Phosphatidylcholine (PC) biosynthesis and degradation - 3 - Sphingolipid metabolism - 5 - Unfolded Protein Response (UPRER) pathway - 10 - Immune response - 13 - Caenorhabditis elegans is a powerful model organism to study dietary effects and the underlying mechanisms - 14 - Materials and Methods - 16 - Caenorhabditis elegans strains - 16 - Bacteria Mixture Assay - 17 - Vitamin B12 supplement on bacteria - 18 - DA1877 bacteria feeding assay - 18 - Worm synchronization - 18 - Oil Red O staining and quantification - 19 - Choline supplement assay - 19 - Western blotting - 20 - Tunicamycin sensitivity assay - 21 - Slow killing assay of Pseudomonas aeruginosa - 22 - Microscopy and quantification of lipid droplets and lysosome-related organelles - 22 - Statistics analysis - 24 - Results - 25 - PC plays a key role in DA1877-mediated lipid reduction through asm-3 - 25 - Sphingosine and C1P are potential metabolites to regulate lipid reduction on DA1877 - 27 - Metabolites involved in ceramide metabolism might induce ER stress in DA1877-fed worms - 29 - Excess PC might not be the cause for DA1877-induced ER stress - 32 - The nutrient vitamin B12 from bacteria DA1877 induces ER stress in the host worms - 34 - Different UPRER pathways are required to trigger ER stress in response to different diets - 35 - DA1877-fed worms are more sensitive to UPRER inducer, tunicamycin - 36 - Worms fed on DA1877 are more susceptible to P. aeruginosa infection - 38 - Discussion - 40 - The role of ASM-3 and C1P in diets-mediated lipid metabolism and ER stress - 40 - ASM-3 and TTM-5 play different roles in diets-mediated lipid metabolism and ER stress - 40 - The relationships between diets-mediated lipid metabolism and ER stress - 42 - DA1877-fed worms have more LROs compared to OP50-fed worms - 42 - MDT-15 differentially regulates ER stress, LROs and lipid content on different diets - 44 - Figures - 46 - Figure 1. PC affect the lipid content in DA1877-fed worms through asm-3 and pcyt-1 - 49 - Figure 2. The metabolite sphingosine and C1P from ceramide metabolism might decrease the lipid content in DA1877-fed worms - 53 - Figure 3. Sphingosine, S1P and C1P might induce DA1877-mediated ER stress - 56 - Figure 4. pcyt-1 and mdt-15 mutants show decreased transcriptional levels of hsp-4 on DA1877 - 59 - Figure 5. The nutrients/metabolites from DA1877 dominantly induce ER stress - 62 - Figure 6. Worms induce ER stress by the similar mechanisms on both diets except for atf-6-mediated sensory pathway on OP50 - 64 - Figure 7. DA1877-fed worms show higher sensitivity to tunicamycin - 67 - Figure 8. Worms fed on DA1877 show more resistance to P. aeruginosa infection on old plates consistently with DA1877-enrichment highlights of our RNA-seq analysis to immune response - 70 - Supplementary - 71 - Supplementary figure. 1 - 71 - Supplementary figure. 2 - 71 - Supplementary figure. 3 - 72 - Supplementary figure. 4 - 72 - Supplementary figure. 5 - 73 - Supplementary figure. 6 - 73 - Supplementary figure. 7 - 75 - Supplementary figure. 8 - 77 - Supplementary figure. 9 - 79 - Supplementary figure. 10 - 81 - Supplementary figure. 11 - 82 - Supplementary figure. 12 - 83 - Supplementary figure. 13 - 86 - Supplementary figure. 14 - 87 - Supplementary figure. 15 - 90 - References - 91 - | |
| dc.language.iso | en | |
| dc.subject | 飲食 | zh_TW |
| dc.subject | 秀麗隱桿線蟲 | zh_TW |
| dc.subject | 脂質 | zh_TW |
| dc.subject | 內質網壓力 | zh_TW |
| dc.subject | 免疫反應 | zh_TW |
| dc.subject | 磷脂膽鹼 | zh_TW |
| dc.subject | 鞘脂 | zh_TW |
| dc.subject | lipid | en |
| dc.subject | diets | en |
| dc.subject | sphingolipid | en |
| dc.subject | C. elegans | en |
| dc.subject | PC | en |
| dc.subject | immune response | en |
| dc.subject | ER stress | en |
| dc.title | 飲食對線蟲脂質代謝、內質網壓力與免疫反應的調控 | zh_TW |
| dc.title | Regulation of lipid metabolism, ER stress and immune responses via bacterial diets 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,脂質,內質網壓力,免疫反應,磷脂膽鹼,鞘脂,飲食, | zh_TW |
| dc.subject.keyword | C. elegans,lipid,ER stress,immune response,PC,sphingolipid,diets, | en |
| dc.relation.page | 106 | |
| dc.identifier.doi | 10.6342/NTU202004107 | |
| 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 | 2025-08-19 | - |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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