請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60067完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳示國 | |
| dc.contributor.author | Chi-Chan Lee | en |
| dc.contributor.author | 李奇展 | zh_TW |
| dc.date.accessioned | 2021-06-16T09:53:59Z | - |
| dc.date.available | 2019-02-08 | |
| dc.date.copyright | 2017-02-08 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-01-09 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60067 | - |
| dc.description.abstract | 環境光線可以透過自主感光視神經細胞 (intrinsically photosensitive retina ganglion cells) 傳遞光線訊息來影響哺乳動物的生理功能。電燈的發明不只影響了人類的生活作息，它更影響了人類的健康狀態。夜晚光線的照射增加了肥胖以及相關代謝疾病的風險。然而，我們對於光線如何引發這些症狀仍的機制仍然不是非常了解。故我們想要利用不同自主感光視神經細胞操弄的小鼠模型搭配上總體基因體學 (metagenomics) 的研究來回答這個問題。我們的研究發現，夜晚光線可以透過視黑質 (melanopsin) 以及自主感光視神經細胞與交感神經之間的迴路來造成老鼠的肥胖、血糖耐受性降低的症狀。同時，也改變了腸道菌的菌落組成、數量以及節律。我們的研究也指出控制腸道節律最重要的原因不是宿主本身的生理時鐘，而是由自主感光視神經細胞所傳遞的光線訊息。綜上所述，本研究顯示光線能夠改變腸道菌的組成，並為夜晚光線如何調控身體代謝提供了一個新的解釋觀點。 | zh_TW |
| dc.description.abstract | Ambient light signal could influence physiological function of mammals through intrinsically photosensitive retina ganglion cells (ipRGCs). The invention of artificial light source not only changes the living style of human but causes serious health problem. Aberrant light information, such as dim light at night (dLAN), enhance the risk of obesity and related metabolic disorders. However, the detailed mechanism of dLAN induced metabolic disorders remains poorly understood. Here, in combination of different ipRGC manipulation mice models and metagenomic analysis, we show that dLAN can induce obesity, hyperglycemia, as well as shift in microbial composition, abundance and oscillations through melanopsin and ipRGC-sympathetic nerve circuit. Furthermore, our data suggest that the zeitgeber information that influence microbial rhythmicity is the photic input from ipRGC but not the circadian rhythm of the host. Together, our results suggest that light could shape the architecture of gut microbiota, which provides a novel mechanism for dLAN-induced metabolic disorders. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T09:53:59Z (GMT). No. of bitstreams: 1 ntu-106-R03b21002-1.pdf: 5269990 bytes, checksum: 0ef626b58c91dcf5371582548672eeec (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 口試委員審定書 i
謝 誌 ii 摘 要 iv Abstract v Contents vi Chapter I Introduction 1 1.1 Impact of artificial light at night on physiological function 1 1.2 Circadian rhythm 2 1.2.1 Molecular clock of circadian rhythm 3 1.2.2 Central and peripheral clock 5 1.2.3 Circadian and metabolism 6 1.3 Intrinsically photo sensitive retina ganglion cells (ipRGCs) 8 1.3.2 Central projections of ipRGCs 10 1.3.3 Subtypes of ipRGCs 11 1.4 Gut microbiota 12 1.4.1 General description of gut microbiota 12 1.4.2 The composition of gut microbiota 14 1.4.3 Gut microbiota in health and disease 14 1.4.4 Gut microbiota and obesity related problems 16 1.4.5 Circadian rhythm and gut microbiota 18 Statement of Purpose 19 Chapter II Materials and Methods 21 2.1 Animals 21 2.2 Genotyping 21 2.2.1 DNA extraction 22 2.2.2 Polymerase chain reaction (PCR) 22 2.3 Experimental design 22 2.4 Metabolism test 24 2.5 Magnetic Resonance Imaging (MRI) fat quantification 24 2.6 Metagenomic library preparation for Illumina sequencing 25 2.6.1 Gut microbe DNA extraction 25 2.6.2 16S metagenomic library preparation 27 2.6.3 Library quality check and pooling 28 2.6.4 Next generation sequencing (NGS) 29 2.7 Microbiota sequence analysis 29 2.7.1 Sequence assembling and classification 29 2.7.2 Composition analysis 31 2.7.3 Diversity analysis 32 2.7.4 Microbe abundance analysis 32 2.7.5 Circadian analysis of microbial oscillations 33 2.8 Quantification of circadian gene expression 34 2.9 Statistical analysis 34 Chapter III Results 35 3.1 Dim light at night induced body weight gain and metabolic disorder in mice 35 3.2 Melanopsin signal and ipRGC circuitry are essential for dLAN induced obesity 36 3.3 Microbiota plays a role in regulation of light-induced metabolic disorders 38 3.4 dLAN influences the gut microbe composition 39 3.5 Melanopsin modulates the effect of dLAN on gut microbiota 41 3.6 ipRGC circuit is necessary for microbial oscillation 43 3.7 Sympathetic nerve system transmit the light information to control metabolic status and gut microbiota 45 3.8 Metabolites may be a potential microbiota-derived signal that influence dLAN-induced symptoms 46 Chapter IV Discussion 49 4.1 Light can directly modulate metabolism independent of circadian and activity shift 49 4.2 Melanopsin through ipRGCs have important functions in regulation of metabolism and microbiota 50 4.3 Light seems to influence obesity and hyperglycemia through distinct pathway 52 4.4 Shift in microbial composition in DTA mice may be caused by desynchronization 53 4.5 Sympathetic nerve may have multiple function in dLAN induced metabolic disorders 54 Significance of the work 57 References 58 Figures 75 Figure 1. Genetic background of the mice used in the study. 75 Figure 2. Experimental scheme and design. 76 Figure 3. Metabolic status of control mice. 77 Figure 4. Glucose metabolism of control mice. 79 Figure 5. Circadian clock gene expression in control mice. 80 Figure 6. Activity patterns of control mice. 81 Figure 7. Metabolic status of melanopsin knockout (MKO) mice. 83 Figure 8. Glucose metabolism of MKO mice. 85 Figure 9. Activity patterns of MKO mice. 86 Figure 10. Metabolic status of ipRGC elimination (DTA) mice. 87 Figure 11. Glucose metabolism of DTA mice. 88 Figure 12. Actogram of DTA mice after two weeks of LD and dLAN. 89 Figure 13. Metabolic status of Opn4Cre/+ ; Brn3bDTA/+ (3bDTA) mice. 91 Figure 14. Glucose metabolism of 3bDTA mice. 92 Figure 15. Summary of metabolic phenotypes of different melanopsin manipulation mice. 93 Figure 16. Quantification of 16S copy number in control mice and antibiotics-treated mice. 94 Figure 17. Metabolic status of antibiotics-treated mice. 95 Figure 18. Glucose metabolism of antibiotics-treated mice. 96 Figure 19. The phylum level relative abundance of gut microbiota from control, MKO, DTA mice. 97 Figure 20. The composition and beta diversity of control mice. 98 Figure 21. Alpha diversity of control mice. 99 Figure 22. Abundance analysis of gut microbiota in control mice. 100 Figure 23. Circadian rhythmicity profile of control mice. 101 Figure 24. Heatmap of the oscillating OTUs in control mice. 102 Figure 25. The composition and beta diversity of MKO mice. 103 Figure 26. Circadian rhythmicity profile of MKO mice. 104 Figure 27. Heatmap of the oscillating OTUs in MKO mice. 105 Figure 28. The composition and beta diversity of control and MKO mice in LD condition. 106 Figure 29. The composition and beta diversity of DTA mice. 107 Figure 30. Circadian rhythmicity profile of DTA mice. 108 Figure 31. Body weight decrease after 6-OHDA injection. 109 Figure 32. Metabolic status of 6-OHDA treated mice. 110 Figure 33. Glucose metabolism of 6-OHDA-treated mice. 111 Figure 34. The composition and beta diversity of 6-OHDA treated mice. 112 Figure 35. Circadian rhythmicity profile of 6-OHDA treated mice. 113 Figure 36. Body weight of propionate-supplement fed mice. 114 Figure 37. Current model of the pathway about dLAN-induced metabolic disorders 115 Tables 116 Table 1. List of primers used in genotyping 116 Table 2. List of primers used in metagenomics sample preparation 116 Table 3. List of primers of Nextera® Index 117 Table 4. Number of sequences after each step of processing 118 Table 5. List of primers of circadian gene quantification 119 Table 6. Serum metabolites of control mice under LD and dLAN condition 120 Appendix Abstract and Poster 123 | |
| dc.language.iso | en | |
| dc.subject | 腸道菌 | zh_TW |
| dc.subject | 總體基因學 | zh_TW |
| dc.subject | 視黑質 | zh_TW |
| dc.subject | 夜晚光線 | zh_TW |
| dc.subject | 生理時鐘 | zh_TW |
| dc.subject | 代謝紊亂 | zh_TW |
| dc.subject | metagenomic sequencing | en |
| dc.subject | melanopsin | en |
| dc.subject | circadian rhythm | en |
| dc.subject | light at night | en |
| dc.subject | metabolic disorders | en |
| dc.subject | gut microbiota | en |
| dc.title | 夜晚光線透過視黑質影響腸道菌相以及身體代謝 | zh_TW |
| dc.title | Dim light at night influence gut microbiota and metabolic status through melanopsin photo detection system | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 于宏燦,陳儀莊,徐志文,廖本揚 | |
| dc.subject.keyword | 腸道菌,視黑質,生理時鐘,夜晚光線,代謝紊亂,總體基因學, | zh_TW |
| dc.subject.keyword | gut microbiota,melanopsin,circadian rhythm,light at night,metabolic disorders,metagenomic sequencing, | en |
| dc.relation.page | 128 | |
| dc.identifier.doi | 10.6342/NTU201700026 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-01-10 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生命科學系 | zh_TW |
| 顯示於系所單位： | 生命科學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-106-1.pdf 未授權公開取用 | 5.15 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。