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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/96333完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林甫容 | zh_TW |
| dc.contributor.advisor | Fu-Jung Lin | en |
| dc.contributor.author | 賴沛襄 | zh_TW |
| dc.contributor.author | Pei-Hsiang Lai | en |
| dc.date.accessioned | 2024-12-24T16:24:01Z | - |
| dc.date.available | 2024-12-25 | - |
| dc.date.copyright | 2024-12-24 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-12-11 | - |
| dc.identifier.citation | 1. Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet, 2024. 403(10431): p. 1027-1050.
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Felicidade, I., et al., Role of 1α,25-Dihydroxyvitamin D3 in Adipogenesis of SGBS Cells: New Insights into Human Preadipocyte Proliferation. Cell Physiol Biochem, 2018. 48(1): p. 397-408. 154. Salehpour, A., et al., 1,25-Dihydroxyvitamin D3 modulates adipogenesis of human adipose-derived mesenchymal stem cells dose-dependently. Nutr Metab (Lond), 2021. 18(1): p. 29. 155. Matsuda, S. and Y. Kitagishi, Peroxisome proliferator-activated receptor and vitamin d receptor signaling pathways in cancer cells. Cancers (Basel), 2013. 5(4): p. 1261-70. 156. Alimirah, F., et al., Crosstalk between the peroxisome proliferator-activated receptor γ (PPARγ) and the vitamin D receptor (VDR) in human breast cancer cells: PPARγ binds to VDR and inhibits 1α,25-dihydroxyvitamin D3 mediated transactivation. Exp Cell Res, 2012. 318(19): p. 2490-7. 157. Savkur, R.S., et al., Coactivation of the human vitamin D receptor by the peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Mol Pharmacol, 2005. 68(2): p. 511-7. 158. Rauluseviciute, I., et al., JASPAR 2024: 20th anniversary of the open-access database of transcription factor binding profiles. Nucleic Acids Res, 2024. 52(D1): p. D174-d182. 159. Malloy, P.J. and B.J. Feldman, Cell-autonomous regulation of brown fat identity gene UCP1 by unliganded vitamin D receptor. Mol Endocrinol, 2013. 27(10): p. 1632-42. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/96333 | - |
| dc.description.abstract | 根據世界衛生組織統計，自2022年起全球約有10億人口受肥胖困擾，而肥胖相關的代謝性疾病已成為重要公共健康問題。肥胖是由於脂肪細胞的過度積聚所致，其中白色脂肪細胞在特定刺激下能褐化為具有較高代謝率的米色脂肪細胞（beige adipocyte），進而改善肥胖及代謝疾病。哺乳期是米色脂肪細胞生成關鍵時期，先前實驗室研究發現在哺乳期給予小鼠酮體前驅物1,3-butanediol（1,3BD）誘導增強哺乳期生酮作用，能促進小鼠成年後米色脂肪細胞生成。然而，增強哺乳期生酮作用是否影響脂肪前驅細胞之組成而導致此現象尚不清楚。本研究第一部分使用單細胞RNA定序（single cell RNA sequencing）分析小鼠iWAT stroma vascular fraction cells（SVFs）之組成。透過R語言分析，我們定義iWAT SVFs共由八種細胞群構成，其中主要四群為相似於幹細胞的adipocyte stromal cells (ASC) 0、前脂肪細胞ASC1及具增生能力的前脂肪細胞ASC2a和ASC2b。我們發現哺乳期增強生酮作用使ASC1細胞群比例增加、ASC0細胞群比例減少，存在ASC0細胞群轉變為ASC1細胞群的可能性，且ASC1細胞群高度表現米色脂肪前驅細胞標記Cd81。因此，ASC1細胞群比例增加可能是哺乳期增強生酮作用促進米色脂肪細胞生成的重要因素之一。此外，轉錄因子vitamin D receptor（VDR）也在ASC1細胞群高度表現，然而活化維生素D訊號途徑是否促進米色脂肪細胞生成仍不清楚。故本研究第二部分擬探討維生素D及活化VDR訊號途徑於米色脂肪生成扮演的角色，同時也想探討維生素D與酮體是否協同促進米色脂肪細胞生成。我們由in vitro模式發現維生素D（calcitriol）在分化期間促進3T3-L1米色脂肪細胞之產熱基因Ucp1表現。且哺乳期長期補充維生素D3（cholecalciferol）能顯著促進小鼠成年後受冷誘導的米色脂肪細胞生成，哺乳期短時間補充維生素D3亦趨勢性促進一般仔鼠（Ch）或肥胖子代（Ob）於P9時的米色脂肪細胞生成。然而在目前實驗設計下未觀察到維生素D與酮體協同促進的效果。綜合以上，本研究發現哺乳期增強生酮作用改變ASCs之組成，進而促進米色脂肪細胞生成，且其中維生素D及VDR訊號途徑可能扮演重要的角色。 | zh_TW |
| dc.description.abstract | Obesity is characterized by the expansion of white adipose tissue with excess accumulation of lipids in white adipocytes. White adipocytes can transition into beige adipocytes under specific stimuli, and beige adipocytes exhibit a higher metabolic rate, offering potential benefits in reducing body weight and improving metabolic health. The preweaning period is crucial for beige adipogenesis. Our previous research demonstrated that administering 1,3-butanediol (1,3BD), a ketone precursor, to preweaning mice enhances beige adipogenesis. However, the impact of 1,3BD on the composition of adipocyte precursor cells remains unclear. In this study, we employed single-cell RNA sequencing to analyze stromal vascular fraction cells (SVFs) isolated from the inguinal white adipose tissue (iWAT) of mice. Using R studio analysis, we identified eight distinct cell clusters based on known cell markers, with four major clusters including stem cell-like adipocyte stromal cells (ASC) 0, preadipocytes ASC1, and proliferative preadipocytes ASC2a and ASC2b. We found that postnatal ketogenesis increases the proportion of ASC1 while decreasing ASC0, suggesting a possible recruitment of ASC1 from ASC0. In addition, the beige progenitor cell marker Cd81 was highly expressed in ASC1, indicating the important role of ASC1 in beige adipogenesis during ketogenesis. Furthermore, the transcription factor vitamin D receptor (VDR) was also highly expressed in ASC1, suggesting a possible involvement of the VDR signaling pathway in beige adipogenesis. Next, we explored the role of vitamin D in beige adipogenesis and determined whether vitamin D and 1,3BD synergistically improve beige adipogenesis. We demonstrated that calcitriol promotes Ucp1 expression in the 3T3-L1 cell line during induction of adipocyte differentiation. Our in vivo experiments further revealed that long-term postnatal vitamin D3 (cholecalciferol) supplementation enhances beige adipogenesis in adult mice. Short-term postnatal vitamin D3 supplementation tends to enhance beige adipogenesis in offspring from both normal diet-fed (Ln) and diet-induced obesity (Ob) dams. However, no significant synergistic effect was observed when both vitamin D and 1,3BD were co-administered at the tested doses. In summary, enhanced ketogenesis during lactation alters the composition of ASCs, promoting beige adipogenesis. Moreover, vitamin D and VDR signaling pathway may play critical roles in regulating this process, offering insights into potential therapeutic strategies for obesity and metabolic disorders. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-12-24T16:24:01Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-12-24T16:24:01Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 謝辭 i
摘要 ii Abstract iv 目次 vi 圖次 ix 表次 xi 縮寫表 xii 第一章 緒論 1 第一節 前言 1 第二節 文獻回顧 2 一、脂肪細胞的種類 2 二、脂肪前驅細胞（adipose precursor cells, APCs） 5 三、單細胞RNA定序（Single cell mRNA sequencing, scRNA-seq） 9 四、酮體之簡介 11 五、維生素D 12 第二章 以單細胞RNA定序探討酮體於脂肪前驅細胞組成的影響 18 第一節 前言與實驗設計 18 一、前言 18 二、實驗設計 19 第二節 材料與方法 20 一、單細胞RNA定序（Single cell RNA sequencing, scRNA-seq） 20 二、ScRNA-seq數據分析 21 三、Gene ontology (GO) analysis 23 第三節 實驗結果 25 一、單細胞RNA定序（scRNA-seq）定義iWAT SVFs存在8種細胞群 25 二、哺乳期增強生酮作用提升脂肪前驅細胞之ASC1細胞群組成 27 三、哺乳期增強生酮作用提升ASC1細胞群之米色脂肪細胞生成標記 28 四、哺乳期增強生酮作用提升轉錄因子Klf9及Vdr於ASC1細胞群之表現量 29 五、哺乳期增強生酮作用提升ASC1細胞群之調控VDR訊號相關基因表現量 29 六、哺乳期增強生酮作用於ASC1細胞群上調之基因參與細胞增生、脂肪分化及脂質代謝相關途徑 30 七、缺乏酮體提升脂肪前驅細胞之鈣離子反應相關基因表現量 31 八、特異性高表現於ASC1細胞群的細胞表面標記 32 第四節 討論 45 一、脂肪前驅細胞群之定義 45 二、小鼠脂肪前驅細胞組成與年齡的關係 46 三、哺乳期增強生酮作用影響脂肪前驅細胞之米色脂肪生成 47 四、哺乳期增強生酮作用提升之轉錄因子KLF9參與調控米色脂肪細胞生成 48 五、脂肪前驅細胞之鈣離子反應與脂肪細胞生成的關係 48 六、米色脂肪前驅細胞的潛在標記 49 七、未來展望 52 第五節 結論 55 第三章 初探維生素D訊號於米色脂肪細胞生成扮演的潛在角色 56 第一節 前言與實驗設計 56 一、前言 56 二、實驗設計 56 第二節 材料與方法 58 一、3T3-L1細胞培養及分化 58 二、人類脂肪細胞培養與分化 60 三、油紅染色（Oil red O staining, ORO staining） 62 四、小鼠飼養 63 五、小鼠體溫量測 64 六、小鼠脂肪組織切片染色 65 七、小鼠脂肪組織均質 67 八、總RNA抽取及反轉錄 67 九、Quantitative Real-time PCR（RT-qPCR） 68 十、統計方法 69 第三節 實驗結果 70 ㄧ、Calcitriol可能在3T3-L1細胞株誘導分化期間促進其米色脂肪細胞分化，但在誘導分化後抑制其米色脂肪細胞分化 70 二、哺乳期長期（19天）補充維生素D3及/或酮體前驅物1,3BD對小鼠成年後米色脂肪細胞生成之影響 71 三、哺乳期短時間（6天）補充維生素D3及/或酮體前驅物1,3BD對P9 Ln仔鼠米色脂肪細胞生成之影響 74 四、哺乳期短時間（6天）補充維生素D3對飲食誘導肥胖母鼠之子代（Ob）米色脂肪細胞生成的影響 76 五、人類脂肪前驅細胞分化 79 第四節 討論 97 一、Calcitriol影響3T3-L1米色脂肪分化的可能原因 97 二、β-adrenergic signaling參與維生素D促進米色脂肪細胞生成機制的可能性 100 三、酮體對米色脂肪細胞生成的影響 100 四、哺乳期短時間補充維生素D3可能促進P9仔鼠的白色脂肪細胞米色化 101 五、哺乳期短時間補充維生素D3不影響P9仔鼠血清25-OHD濃度的可能原因 102 六、哺乳期短時間補充維生素D3活化仔鼠iWAT VDR訊號的效果可能不顯著 104 七、哺乳期短時間補充維生素D3可能改善P9 Ob仔鼠的非酒精性脂肪肝 105 八、VDR蛋白或其訊號活化於米色脂肪生成扮演重要的角色 105 九、以VDR-KO小鼠探討VDR訊號於米色脂肪細胞生成的可行性 106 十、人類脂肪前驅細胞分化 108 十一、VDR及其訊號促進米色脂肪細胞生成的潛在機制 108 十二、未來展望 112 第五節 結論 115 總結 116 附錄 117 參考文獻 123 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 脂肪前驅細胞 | zh_TW |
| dc.subject | 哺乳期生酮 | zh_TW |
| dc.subject | 米色脂肪細胞生成 | zh_TW |
| dc.subject | 維生素D | zh_TW |
| dc.subject | VDR | zh_TW |
| dc.subject | 單細胞RNA定序 | zh_TW |
| dc.subject | VDR | en |
| dc.subject | beige adipogenesis | en |
| dc.subject | adipose stromal cells | en |
| dc.subject | postnatal ketogenesis | en |
| dc.subject | single cell RNA sequencing | en |
| dc.subject | vitamin D | en |
| dc.title | 探討酮體誘導米色脂肪細胞重塑的複雜性及維生素D訊號扮演的潛在角色 | zh_TW |
| dc.title | Unraveling the complexity of beige remodeling induced by ketone bodies reveals vitamin D signaling as a potential mediator | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 黃青真;謝博軒;王志豪;李家瑋 | zh_TW |
| dc.contributor.oralexamcommittee | Ching-Jang Huang;Po-Shiuan Hsieh;Chih-Hao Wang;Chia-Wei Lee | en |
| dc.subject.keyword | 米色脂肪細胞生成,脂肪前驅細胞,哺乳期生酮,單細胞RNA定序,維生素D,VDR, | zh_TW |
| dc.subject.keyword | beige adipogenesis,adipose stromal cells,postnatal ketogenesis,single cell RNA sequencing,vitamin D,VDR, | en |
| dc.relation.page | 133 | - |
| dc.identifier.doi | 10.6342/NTU202404686 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2024-12-11 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科技學系 | - |
| dc.date.embargo-lift | 2029-12-10 | - |
| 顯示於系所單位： | 生化科技學系 | |
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