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DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 丁詩同(Shih-Torng Ding) | |
dc.contributor.author | Yu-Jen Chen | en |
dc.contributor.author | 陳郁仁 | zh_TW |
dc.date.accessioned | 2021-05-20T00:51:50Z | - |
dc.date.available | 2021-02-20 | |
dc.date.available | 2021-05-20T00:51:50Z | - |
dc.date.copyright | 2021-02-20 | |
dc.date.issued | 2021 | |
dc.date.submitted | 2021-02-05 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8311 | - |
dc.description.abstract | 成人與小鼠具顯而易見之棕色脂肪,且經由冷刺激下,某些白色脂肪部位可發現具類似棕色脂肪之細胞,此過程稱為白色脂肪棕色化 (white fat browning) 或該棕色化之白色脂肪細胞被稱作米色脂肪細胞 (beige adipocyte) 。活化棕色脂肪或增加白色脂肪棕色化/米色脂肪可增加產熱以促進能量消耗,具抵抗肥胖或治療糖尿病之潛能。脂締素 (adiponectin) 為脂肪組織分泌之細胞激素,可調控全身代謝。於高脂飼糧下,脂締素可藉由增加白色脂肪堆積以減少游離脂肪酸於其他器官之傷害與堆積,進而改善肥胖造成之胰島素阻抗。然而,脂締素與其受體 (adiponectin receptors) 對冷刺激下棕色脂肪之活性與白色脂肪棕色化之功能仍未全然了解。首先,本實驗先改良脂肪幹細胞分離之流程,增加產量與效率,並且建立條件可以分化出白色與米色脂肪細胞以進行後續實驗。另外,此研究並建立FVB小鼠品系下,冷刺激對該FVB品系小鼠,低溫處理之強度及時間長度。接著利用此條件探討野生型 (wild-type) 小鼠與基因轉殖小鼠大量表現脂締素受體一型 (adiponectin receptor 1; AdipoR1) ,於冷刺激下棕色脂肪與白色脂肪棕色化之活性與功能。本研究利用3D正子掃描 (positron emission tomography/computed tomography, PET/CT scanning) 發現,AdipoR1小鼠於冷刺激下葡萄糖之攝入較WT小鼠少,棕色脂肪與米色脂肪之脂肪細胞大小較大,並有小鼠全身體表溫度或棕色脂肪部位表面溫度較低之情形,此現象皆顯示AdipoR1小鼠產熱功能可能較低。另外,棕色或米色脂肪組織中生熱蛋白基因 (uncoupling protein 1, Ucp1) 與棕色脂肪標記 (brown adipocyte marker) 基因、棕色脂肪細胞粒線體基因標記、脂肪分解基因、脂肪氧化基因於棕色或米色脂肪組織中也較WT小鼠低。此外,AdipoR1小鼠所分離出白色脂肪幹細胞分化之米色脂肪細胞,其產熱基因Ucp1與棕色脂肪標記基因、棕色脂肪細胞粒線體基因標記基因,皆較WT小鼠之脂肪幹細胞分化之米色脂肪低。因此,本研究發現AdipoR1減少冷刺激誘導下棕色脂肪與米色脂肪之生熱功能 (cold-induced thermogenesis) ,調節脂締素或其受體功能或調控其下游途徑可能為日後肥胖與相關疾病治療之契機。 | zh_TW |
dc.description.abstract | Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activation of thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing “healthy obese” by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors and signaling, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. First, we streamlined the isolation process for purifying high quality adipose stem cells that are able to differentiate into white or beige adipocytes from different species such as human, pig or mice. Next, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [18F] fluorodeoxyglucose-PET/CT (18F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression related to thermogenic Ucp1, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic Ucp1, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis. | en |
dc.description.provenance | Made available in DSpace on 2021-05-20T00:51:50Z (GMT). No. of bitstreams: 1 U0001-0502202115453500.pdf: 58623506 bytes, checksum: ccb9fd8c08d2ff868a7d1cbaeef79156 (MD5) Previous issue date: 2021 | en |
dc.description.tableofcontents | 致謝 ii 中文摘要 iv Abstract vi Table of contents viii List of figures xi List of tables xiii Chapter 1 Literature review 1 Obesity-associated inflammation 3 N-3 PUFA and their anti-inflammatory effects 5 N-3 PUFA suppress cytokine-induced inflammation to reduce obesity-related responses. 8 GPR120 mediates the anti-inflammatory and insulin-sensitizing actions of DHA 9 Involvement of FoxO in inflammatory responses 11 Processes elevating classical brown adipose or beiging of white adipose tissue activity 15 Orchestration of adipose inflammation and thermogenesis in BAT/white adipose browning 16 Alternative activated macrophages (AAM) on browning of white adipose tissues 17 Role of FoxO in classical brown and beige adipogenesis 18 PUFA on browning/beiging of white adipocytes 24 Future perspective 27 Chapter 2 Specific Aim 29 Chapter 3 Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice 30 Introduction 30 Materials and Methods 34 Animals and diets 34 Cold-acclimation procedure 35 Sample collection and preparation 36 PET/CT scanning 36 Histological analysis by H E stain 37 Depot surface temperature measurements and thermographic imaging 37 Gene expression analysis by qPCR 38 Cell culture for isolation and differentiation of mouse stromal/vascular cells into mature adipocytes 39 Statistical analysis 40 Results 43 Enhanced body-weight losses in AdipoR1 mice during cold exposure 44 Diminished cold-induced glucose uptake by PET/CT scanning in classical BAT and browned supWAT of AdipoR1 mice 46 Enlarged adipocyte size in classical BAT and browned iWAT of AdipoR1 mice 48 Decreased surface depot temperature and surface body temperature in cold-induced AdipoR1 mice 50 Increased adipose expression of adiponectin, adiponectin receptors, and brown adipocyte markers in WT female mice versus WT male mice under cold exposure 52 Reduced adiponectin and adiponectin receptors in adipose tissues of AdipoR1 female mice versus WT female mice under cold exposure 56 Decreased brown-adipocyte selective markers in classical BAT and browned iWAT of AdipoR1 female mice under cold exposure 58 Decreased expression of glucose uptake, lipolysis, and fatty acid oxidation genes in classical BAT and browned iWAT of AdipoR1 mice under cold exposure 61 Decreased expression of browning genes and enhanced whitening genes in classical BAT and browned iWAT of AdipoR1 mice after cold exposure 64 Decreased brown adipocytes markers in differentiated beige adipocytes isolated from iWAT of AdipoR1 mice 67 Discussion 70 PET/CT and cold-induced glucose uptake 70 BAT and cold-induced glucose uptake 73 Adiponectin/AdipoR1 on modulating BAT and browned WAT 74 Conclusion 80 Chapter 4 Isolation and differentiation of adipose-derived stem cells from porcine subcutaneous adipose tissues 81 Introduction 81 Materials and equipment 83 Protocol 85 Representative results 100 Discussion 106 References 110 Appendix I 141 Publication list 141 Appendix II 143 Curriculum Vitae 143 | |
dc.language.iso | en | |
dc.title | 過度表現脂締素受體一型抑制小鼠棕色與米色脂肪之活性 | zh_TW |
dc.title | Overexpression of adiponectin receptor 1 inhibits brown and beige adipose tissue activity in mice | en |
dc.type | Thesis | |
dc.date.schoolyear | 109-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 歐柏榮(Bor-Rung Ou),陳洵一(Shuen-Ei Chen),林劭品(Shau-Ping Lin),林原佑(Yuan-Yu Lin),余祺(Chi Yu) | |
dc.subject.keyword | 脂締素,脂締素受體一型,米色脂肪,棕色脂肪,正子掃描,生熱作用,生熱蛋白一型, | zh_TW |
dc.subject.keyword | adiponectin,adiponectin receptor 1,beige adipose tissue,brown adipose tissue,cold-induced thermogenesis,PET/CT scintigraphy,uncoupling protein 1 (UCP1), | en |
dc.relation.page | 148 | |
dc.identifier.doi | 10.6342/NTU202100596 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2021-02-08 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物科技研究所 | zh_TW |
顯示於系所單位: | 生物科技研究所 |
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