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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蘇剛毅(Kang-Yi Su) | |
| dc.contributor.author | Chiu-En Lin | en |
| dc.contributor.author | 林裘恩 | zh_TW |
| dc.date.accessioned | 2022-11-25T07:45:52Z | - |
| dc.date.available | 2023-08-31 | |
| dc.date.copyright | 2021-09-16 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-19 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82503 | - |
| dc.description.abstract | "隨著生活習慣改變與飲食的精緻化，肥胖等代謝性疾病，漸漸成為最為普遍並受矚目的健康議題，研究脂肪組織調控代謝的議題，是我們感興趣的。 人體脂肪組織按照分佈位置與功能可以分為：白色脂肪(White)、棕色脂肪(Brown)，白色脂肪為人體主要儲存多餘能量的場所，透過三酸甘油質的型態將多餘能量儲存，需要時再分解、釋放，白色脂肪主要分布於皮下與臟器周圍，因此也有隔熱與保護臟器等功能；棕色脂肪是身體重要的產熱器官，透過UCP1表達，產出熱能維持體溫，同時增強葡萄糖的利用與脂肪分解；白色脂肪也有產熱的功能，當身體受到冷刺激時，去甲基腎上腺素便會分泌刺激白色脂肪棕化，形成在形態和功能上都和棕色脂肪相似的棕化(Beige)細胞。 近期許多研究證明，刺激體內棕化細胞生成或活化棕色脂肪，都能有效調控身體代謝，促進血糖與脂肪代謝，進而達到減肥的效果。在過去實驗室的研究中，我們發現HLJ1剔除小鼠的白色脂肪組織相較於野生型有較大的油滴，而在受到冷刺激時，白色脂肪組織棕化現象較為明顯，產熱基因Ucp1較WT小鼠表現量高，我們也透過RNA-seq資料進行GSEA和MetaCore分析，發現HLJ1剔除小鼠的白色脂肪組織，在脂肪生成和氧化途徑相關基因表現較WT高，種種結果證明HLJ1參與在脂肪生成和產熱功能當中，但機制尚未釐清，因此本篇研究專注在，探討HLJ1與脂肪生成以及產熱功能的機制研究。 我們利用primary iWAT preadipocyte, primary BAT preadipocyte, 3T3-L1三種脂肪幹細胞建立脂肪細胞分化模型，在三種模型中都可以發現，相較於野生型細胞株，HLJ1默化的細胞中有較高比例的幹細胞分化為成熟脂肪細胞，接著透過基因表現和蛋白表達量證明，HLJ1表達減少會促進轉錄因子PPARγ表達與活化，並刺激下游脂肪生成相關基因轉錄：Leptin, Glut4, AdipoQ隨之上升。我們進一步探討HLJ1對PPARγ的調控機轉，發現HLJ1缺失的細胞胰島素訊號途徑活化較不明顯，而mTOR表現量卻增加，推測HLJ1缺失透過某種機制促進mTOR以及PPARγ表達，而負向回饋抑制胰島素訊號傳遞途徑，進而對生物體造成脂肪組織增生以及胰島素抗性升高等影響。另一方面，HLJ1缺乏也促使粒線體生成基因Pgc1α表達增加，所生成的脂肪細胞相較於HLJ1表現正常的脂肪細胞具有較高的產熱基因(Ucp1)表現，而細胞功能上，粒線體功能、脂肪分解與產熱功能、醣類代謝功能等仍待進一步實驗釐清。 " | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T07:45:52Z (GMT). No. of bitstreams: 1 U0001-1708202115374400.pdf: 15919065 bytes, checksum: 2529fe640a947d0ce2fcfb2f07484cbe (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 致謝 3 中文摘要 4 Abstract 6 ABBREVIATION 7 Chapter 1 Introduction 12 Obesity 13 Adipose tissue 13 Adipose tissue expansion 14 Molecular mechanisms of adipogenesis 14 The Role of Peroxisome Proliferator-Activated Receptors in Adipogenesis 15 The Role of PPAR gamma in Adipocyte Differentiation. 16 PPAR gamma Phosphorylation and Physiology 17 Insulin signaling in preadipocyte 17 Insulin signaling in adipocyte 18 Impact of mTOR on lipogenesis. 18 The role of MAPKs in adipogenesis 19 Adipokines 20 Thermogenesis 20 Regulation of Adipocyte Thermogenesis 21 Biological Functions of Thermogenic Adipose Tissues 22 Heat shock protein 22 Heat shock protein 40 (DNAJB4) 23 Chapter 2 Specific Aim 24 Chapter 3 Materials and Methods 26 3.1 Animals 27 3.2 Isolation of primary White and Brown preadipocytes 27 3.3 Differentiation of primary preadipocytes 28 3.4 Cell culture 28 3.5 3T3L1 differentiation into adipocyte 29 3.6 Establishment of Thermogenic Adipocyte. 29 3.7 Oil red O staining 29 3.8 LipdTOX staining 30 3.9 RNA extraction and real-time PCR 30 3.10 Protein Extraction and Western Blotting 31 3.11 MTT assay 32 3.12 Lentivirus titration and transduction 32 3.13 Generating single HLJ1 stable silencing 3T3L1 with Lentivirus 33 3.14 Cell Transfection 33 3.15 Insulin Signaling Study 33 3.16 Lipolysis Assay 34 3.17 Statistical Analysis 34 Chapter 4 Results 35 4.1 Differentiation of mature adipocyte from preadipocytes 36 4.2 HLJ1 is Highly Express During Adipogenesis. 36 4.3 Depletion of HLJ1 promotes lipid accumulation in cultured iWAT adipocytes. 37 4.4 Generation of Stable Lentivirus-mediated HLJ1-silencing 3T3L1 preadipocyte 38 4.5 Reduction of HLJ1 increased adipogenesis in 3T3L1. 38 4.6 Absent of HLJ1 in brown preadipocyte has an increased differentiation efficiency. 39 4.7 Insulin signaling and HLJ1 39 4.8 Investigation of Thermogenic Function in HLJ1 Depletion Adipocytes. 41 Chapter 5 Discussions 44 5.1 HLJ1 and Lipid Accumulation 45 5.2 Indeterminate gene regulation in primary iWAT adipocyte. 45 5.3 PPARγ activity and Adipocyte Size 46 5.4 Enhanced Adipogenesis or Insulin Resistant 47 Chapter 6 Figures 50 6.1 GSEA compared iWAT samples from HLJ1 KO (red) against WT (blue) mice. 51 6.2 Differentiation of Mature Adipocyte from Preadipocytes 55 6.3 HLJ1 is highly Expressed During Adipogenesis. 57 6.4 Depletion of HLJ1 promotes lipid accumulation in cultured iWAT adipocytes. 58 6.5 Generation of Stable Lentivirus-mediated HLJ1-silencing 3T3L1 preadipocyte. 60 6.6 Reduction of HLJ1 increased adipogenesis in 3T3L1. 61 6.7 Absent of HLJ1 in brown preadipocyte has an increased differentiation efficiency. 64 6.8 Insulin signaling pathway and HLJ1 65 6.9 Investigation of Thermogenic Function in HLJ1 depletion adipocytes. 70 6.10 Investigation of lipolysis ability of HLJ1 depletion adipocyte. 72 Chapter 7 Tables 74 Table 1. Primer Sequences Used in Quantitative PCR Test. 75 Table.2 Antibodies Used in Western Blotting. 76 References 77 | |
| dc.language.iso | en | |
| dc.title | 探討 HLJ1 蛋白在脂肪組織生成與產熱功能所扮演之角色與機制 | zh_TW |
| dc.title | Investigate the Role of HLJ1 in Adipose Tissue Adipogenesis and Thermogenesis | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 郭靜穎(Hsin-Tsai Liu),林亮音(Chih-Yang Tseng),楊雅倩 | |
| dc.subject.keyword | HLJ1,脂肪細胞,脂肪分化,脂肪產熱,胰島素訊號, | zh_TW |
| dc.subject.keyword | HLJ1,Adipocyte,Adipogenesis,Thermogenesis,Insulin signaling, | en |
| dc.relation.page | 87 | |
| dc.identifier.doi | 10.6342/NTU202102434 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-19 | |
| 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 |
| dc.date.embargo-lift | 2023-08-31 | - |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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