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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蘇剛毅(Kang-Yi Su) | |
| dc.contributor.author | Wan-Yi Huang | en |
| dc.contributor.author | 黃琬儀 | zh_TW |
| dc.date.accessioned | 2021-06-17T01:46:54Z | - |
| dc.date.available | 2022-09-12 | |
| dc.date.copyright | 2017-09-12 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-07-26 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67736 | - |
| dc.description.abstract | 小分子核醣核酸(Micro RNA, miRNA)是一段長度約22個核苷酸的RNA分子，目前已被證實會透過和目標基因的結合影響其表達。本次研究所探討的miR-137，除了已知在腦部具有很高的表現量，並會參與神經元的分化與成熟，已經有團隊透過全基因組關聯分析(Genome-wide association analysis, GWAS)發現和神經官能症(Schizophrenia)相關的單核苷酸多型性(Single-nucleotide polymorphism, SNP)就位於miR-137的上游，另外也有許多文獻探討miR-137在癌症所扮演的角色，像是在非小細胞肺癌(Non-small cell lung cancer, NSCLC)中被認為可以用來預測病人具有不好的預後。miR-137廣泛地參與許多生物體的作用，於是我們以此為基礎，想要進一步在動物模型探討miR-137的生理意義。首先我們針對小鼠的各個重要器官進行miR-137表現量之剖析，發現前三高表現量的器官分別是大腦、心臟及肝臟，考量實驗室所擁有的方法學，我們選擇阿黴素（Doxorubicin）、乙醯胺酚（Acetaminophen）、脂多醣（Lipopolysaccharide）、高油脂飼料（High-fat diet）分別針對心臟及肝臟（後三者）給予小鼠短期壓力，結果發現只有在經過一個月的高油脂飼料的餵食後，小鼠肝臟的miR-137表現量顯著地下降了。而在先前實驗室所製作出的miR-137基因全身剔除小鼠(whole-body homozygous miR-137 knockout mice)的觀察中，已知Knockout (miR-137-/-)小鼠大約在出生後21天死亡，且有嚴重的生長遲緩現象，在隨機血糖的測量上，Wild-type (miR-137+/+)、Heterozygous (miR-137+/-)、Knockout小鼠呈現高中低的趨勢，透過組織染色發現Knockout小鼠的脂肪細胞嚴重萎縮(Adipose atrophy)。根據上述的初步結果，我們認為miR-137可能與小鼠的生理代謝有關，而由於Knockout小鼠早夭的特性，本次研究是以Heterozygous老鼠為主，以一般飼料（Regular diet; RD）飼養到七周大成鼠時，依據實驗設計再給予特定組別高油脂飼料（High-fat diet; HFD），是一種常見在活體實驗中給予代謝壓力的實驗策略。首先在全程餵食一般飼料的組別中，Heterozygous小鼠體重上升的較多，但攝食量並沒有顯著差異，血清中的三酸甘油脂和肝臟中的脂肪酸氧化(β-oxidation)的決定速率酵素Cpt1a 表現量則比起控制組更高，表示miR-137的減少確實對於小鼠的代謝產生了影響。進一步我們給予小鼠HFD，一開始在不限制HFD飲食量的組別中，Heterozygous小鼠體重上升的較多，但攝食量也比起控制組更高，暗示了miR-137和小鼠食慾的關係。而進一步針對小鼠的代謝，給予相同量的HFD (Pair-feeding)，發現Heterozygous小鼠的增重幅度並沒有如預期地和控制組有所不同，表示這個根據這個實驗策略，不同基因型（Genotype）小鼠的代謝並沒有差異。。
結果顯示，在活體中miR-137的減少除了影響小鼠的代謝，也影響了小鼠對於高油脂飼料的食慾，我們也期待miR-137能成為具有潛力的調控代謝及食慾的指標，甚至有朝一日能應用於代謝症候群的治療上，進而改善族群的健康。 | zh_TW |
| dc.description.abstract | MicroRNA is a class of non-coding RNA which is about 22 nucleotides long and has been widely studied in the regulation of gene expression. Recent studies revealed that miR-137 plays a potential role in neural development and cancer biology. However, the direct investigation in vivo for miR-137 is still rare. In the first, we had validated the top three miR-137 highly-expressed organs: brain, heart and liver. According to the accessible material in our lab, we chose doxorubicin, acetaminophen, lipopolysaccharide and high-fat diet as a short-term stress to affect miR-137 expression. Only high-fat diet feeding for 1 month downregulated the expression level of miR-137 in mouse liver. Besides, we had generated whole-body homozygous miR-137 knockout mice (miR-137-/-), and observed that miR-137-/- mice were died around 21-days-old with dramatic growth retardation. The random blood glucose was measured in a lower trend between the wild-type (miR-137+/+), heterozygous knockout (miR-137+/-) and miR-137-/- mice. In addition, the adipose tissue was severely atrophy in the miR-137-/- mice. We hypothesized that miR-137 would affect the physiological metabolism, and focused on miR-137+/- adult mice for our research. First, during regular diet-feeding, miR-137+/- mice gained much weight with no significantly different amount of food intake. Serum triglyceride and Cpt1a mRNA expression level were elevated in miR-137+/- mice compared to the wild-type control. Thus, miR-137 deficiency has impact on mouse basal metabolism. Furtherly, we subjected mice to a high-fat diet (HFD), which was commonly used as metabolism stress. With the ad libitum HFD-feeding, we found that miR-137+/- ate more HFD with heavier body weight compared to the wild-type control, linking miR-137 and appetite for the first time. We then introduced pair HFD-feeding to mice targeting for metabolism, but results indicated that there was no difference in metabolism between genotypes based on this strategy.
In conclusion, miR-137 may play a role in both metabolism and appetite in vivo. We expect that miR-137 may be a potential marker for regulation of metabolism and appetite and a useful therapeutic target applied in the metabolic disease. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T01:46:54Z (GMT). No. of bitstreams: 1 ntu-106-R04424025-1.pdf: 1567823 bytes, checksum: d8e170011cbb1951ba49aaaec087c14c (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 口試委員會審訂書 I
誌謝 II 中文摘要 IV ABSTRACT VI 1. INTRODUCTION 1 1.1 MicroRNA 1 1.2 miR-137 2 1.2.1 miR-137 in neurology 2 1.2.2 miR-137 in oncology 5 1.3 Fatty acid metabolism 6 1.4 Appetite 8 1.5 Specific aim 9 1.6 Study design 9 1.6.1 Short-term stress based on the previous profile 9 1.6.2 HFD, a metabolism stress to miR-137+/- mice 12 2. MATERIALS AND METHODS 14 2.1 MiR-137 knockout mice model 14 2.1.1 Animals keeping 14 2.1.2 Tail DNA extraction and genotyping 14 2.2 Short-term stress on wild-type mice 15 2.2.1 Doxorubicin injection 16 2.2.2 Acetaminophen injection 16 2.2.3 Lipopolysaccharide injection 17 2.2.4 High-fat diet feeding 17 2.3 Long-term high fat-diet feeding 17 2.4 Sample preparation 18 2.4.1 Blood collection and mice sacrificing 18 2.4.2 Real-time quantitative RT-PCR 18 2.5 Pathology interpretation 20 2.6 Body composition analysis 20 2.7 Home cage activity 20 2.8 Food and water intake analysis 21 3. RESULTS 22 3.1 Mice model confirmation 22 3.2 miR-137 expression level after short-term stress 22 3.3 Whole-body deletion of MiR-137 in mice alters the phenotype. 23 3.4 miR-137+/- mice show no significant difference in body composition analysis. 24 3.5 miR-137+/- mice spend more time eating and drinking in the twenty-four hour activity analysis during regular diet-feeding. 24 3.6 miR-137+/- mice gain weight faster than wild-type mice during regular diet-feeding. 25 3.7 miR-137+/- mice gain weight faster than wild-type mice during ad libitum high-fat diet-feeding. 25 3.8 miR-137+/- mice have no significant altered phenotype in pair high-fat diet-feeding compared to the wild-type control. 26 3.9 Cpt1, the rate-limiting marker of FA oxidation, is upregulated in miR-137+/- mice during RD-feeding. 27 4. CONCLUSIONS 28 5. DISCUSSIONS 30 5.1 miR-137 knockout mice in this study 30 5.2 Animal housing to the home cage analysis 31 5.3 The short-term stress to mouse 32 5.4 miR-137 to appetite 32 5.5 Rebounding of miR-137 expression level in wild-type mice for 2 months HFD-feeding 33 5.6 Upregulated Cpt1a mRNA and decreased fat mass in miR-137+/- mice 33 5.7 Upregulated Acc mRNA in miR-137+/- after pair HFD-feeding 34 5.8 miR-137 in metabolism 34 6. Figure 37 7. TABLES 50 8. REFERENCE 51 SUPPLEMENTARY DATA 65 APPENDIX 67 | |
| dc.language.iso | en | |
| dc.subject | 小分子核糖核酸-137 | zh_TW |
| dc.subject | 基因剔除鼠 | zh_TW |
| dc.subject | 食慾 | zh_TW |
| dc.subject | 代謝 | zh_TW |
| dc.subject | 高油脂飼料 | zh_TW |
| dc.subject | high-fat diet | en |
| dc.subject | appetite | en |
| dc.subject | miR-137 | en |
| dc.subject | metabolism | en |
| dc.subject | knockout mice | en |
| dc.title | 小分子核糖核酸-137對食慾及代謝之影響造成小鼠體重增重 | zh_TW |
| dc.title | The Impact of miR-137 on Appetite and Metabolism Caused Body Weight Gain | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林亮音(Liang-In Lin),楊雅倩(Ya-Chien Yang),張以承(Yi-Cheng Chang) | |
| dc.subject.keyword | 小分子核糖核酸-137,基因剔除鼠,高油脂飼料,代謝,食慾, | zh_TW |
| dc.subject.keyword | miR-137,knockout mice,high-fat diet,metabolism,appetite, | en |
| dc.relation.page | 70 | |
| dc.identifier.doi | 10.6342/NTU201702001 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-07-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-106-1.pdf 未授權公開取用 | 1.53 MB | Adobe PDF |
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