請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94990完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 潘敏雄 | zh_TW |
| dc.contributor.advisor | Min-Hsiung Pan | en |
| dc.contributor.author | 董立敏 | zh_TW |
| dc.contributor.author | Li-Min Tung | en |
| dc.date.accessioned | 2024-08-23T16:19:22Z | - |
| dc.date.available | 2024-08-24 | - |
| dc.date.copyright | 2024-08-23 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-08-09 | - |
| dc.identifier.citation | Ali, A. T.; Hochfeld, W. E.; Myburgh, R.; Pepper, M. S. Adipocyte and adipogenesis. Eur J Cell Biol. 2013, 92, 229-236.
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Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest. 2013, 123, 3404–3408. Yoon, H. S.; Cho, C. H.; Yun, M. S.; Jang, S. J.; You, H. J.; Kim, J. H.; Han, D.; Cha, K. H.; Moon, S. H.; Lee, K.; Kim, Y. J.; Lee, S. J.; Nam, T. W.; Ko, G. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat. Microbiol. 2021, 6, 563–573. Zhao, J.; Yang, Q.; Zhang, L.; Liang, X.; Sun, X.; Wang, B.; Chen, Y.; Zhu, M.; Du, M. Ampkalpha1 deficiency suppresses brown adipogenesis in favor of fibrogenesis during brown adipose tissue development. Biochem Biophys Res Commun. 2017, 491, 508–514. Zhao, X.; Wang, M. H.; Wen, Z. T.; Lu, Z. H.; Cui, L. J.; Fu, C.; Xue, H.; Liu, Y. F.; Zhang, Y. Glp-1 receptor agonists: Beyond their pancreatic effects. Front. Endocrinol. 2021, 12. Zolkiewicz, J.; Marzec, A.; Ruszczynski, M.; Feleszko, W. Postbiotics-a step beyond pre- and probiotics. Nutrients. 2020, 12. Zuriaga, M. A.; Fuster, J. J.; Gokce, N.; Walsh, K. Humans and mice display opposing patterns of "browning" gene expression in visceral and subcutaneous white adipose tissue depots. Front Cardiovasc Med. 2017, 4. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94990 | - |
| dc.description.abstract | 肥胖現今已是全球性的代謝疾病，過量脂肪蓄積可能造成心血管疾病，因此研究改善肥胖的手段是重要的議題。植化素預防肥胖的分子機制當中，包含了調控食慾、誘發米色與棕色脂肪非顫抖性產熱作用 (non-shivering thermogenesis, NST)，以及調節腸道菌相 (gut microbiota, GM)。山竹子素 (garcinol) 是一由印度鳳果 (Garcinia indica) 分離出的植化素。已有文獻證實garcinol 可降低組蛋白去乙醯酶11 (histone deacetylase 11, HDAC11) 的催化活性；先前文獻亦證實 HDAC11 的表現量與肥胖呈正相關、且與 NST 活性呈負相關。本實驗室先前研究指出，餵食 C57BL/6 小鼠混入 garcinol 粉末的飼料，可透過調節脂肪細胞相關因子表現量、增加 GM 中 Akarnania muciniphila 比例，減緩高脂飲食誘導的肥胖。因此，本研究將進一步探討降低 HDAC11 活性、促進 NST 活化與增加 GM 代謝物短鏈脂肪酸 (short chain fatty acids, SCFAs)，是否為 garcinol 抗肥胖的分子機制。本研究的動物實驗中，給予 0.25% 的 garcinol 具有減少攝食量並減緩攝食高脂飲食小鼠體重上升的效果，此現象可能與血清中升高的類升糖素胜肽-1 (Glucagon-like peptide-1, GLP-1) 與降低的瘦素 (leptin) 相關。garcinol 介入能有效降低肝臟重量，在 H&E 染色的影像中也能觀察出減少油滴累積的現象。另外，在白色脂肪相關實驗數據中，可觀察到 garcinol 顯著降低其重量與細胞粒徑大小，western blot 結果顯示，促進 ACC 磷酸化和 ATGL 蛋白表現量為其中機轉。經實驗測定，garcinol 使糞便中的丙酸 (propionic acid) 及丁酸 (butyric acid) 含量顯著增加。在細胞實驗模式下，3T3-L1 脂肪細胞在15 μM garcinol 介入後，不但能從油紅染色實驗觀察到油滴蓄積顯著降低，亦能從蛋白表現量的分析中得知 garcinol 透過活化 AMPK 促進 UCP1 與 PRDM16 之表現。綜上所述，本研究證實 garcinol 可透過抑制食慾、調節脂肪細胞代謝與促進 GM 生成 SCFAs，達到抗肥胖的效果。 | zh_TW |
| dc.description.abstract | Obesity is a global metabolic disease characterized by dysfunctional adipose tissue. Many phytochemicals prevent obesity by enhancing satiety, inducing non-shivering thermogenesis (NST) in adipocytes and regulating gut microbiota (GM) composition. garcinol, a polyisoprenylated benzophenone compound isolated from Garcinia indica, has been proven to inhibit histone deacetylase 11 (HDAC11), which positively correlates with obesity with its NST downregulating ability. A previous study also indicated garcinol could curb high-fat diet (HFD)-induced obesity in mice by affecting the expression of adipose associated factors and increasing Akkermansia muciniphila in GM. Whereas, whether garcinol exerts its anti-obesity ability via binding HDAC11, activating NST and increasing short-chain fatty acids (SCFAs) needs further research. Therefore, we aim to study the underlying anti-obesity molecular mechanisms of garcinol, especially lipids metabolism and NST activity in adipocytes and SCFAs generated by GM in mice.
Our results show that 0.25% oral garcinol supplementation significantly decreases body weight and energy intake with higher GLP-1 and lower leptin levels in serum. garcinol reduces lipids accumulation in liver, and decreases the sizes of white adipocytes by upregulating phosphorylation levels of ACC and ATGL expressions in HFD-induced obese mice. Additionally, garcinol also increases fecal propionic and butyric acids. In vitro experiments indicate less triglyceride accumulation, and upregulate UCP1 and PRDM16 protein expression by AMPK activation within adipocytes with a 15 μM garcinol intervention in 3T3-L1 adipocytes. In conclusion, our study demonstrates that garcinol prevents obesity by suppressing appetite, modulating adipocyte metabolism and enhancing SCFAs synthesis. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-23T16:19:22Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-23T16:19:22Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 I
謝辭 II 中文摘要 IV Abstract V 目次 VII 圖次 XI 表次 XIII 附圖次 XIV 縮寫表 XV 第一章、緒論 1 第二章、文獻回顧 3 第一節、肥胖 3 一、流行病學定義與盛行率 3 二、肥胖的成因與高脂飲食 (High-fat diet, HFD) 5 三、肥胖與脂肪代謝異常 6 四、肥胖的危害及預防治療手段 6 五、膳食因子抗肥胖的機制 7 六、肥胖與腸道菌相代謝物 8 第二節、脂肪組織與脂肪細胞株 11 一、脂肪組織之生理功能 11 二、脂肪組織之種類 13 三、3T3-L1 脂肪細胞株 15 四、非顫抖性產熱 (Non-shivering thermogenesis, NST) 16 第三節、組蛋白去乙醯酶 11 (Histone deacetylase 11, HDAC11) 19 一、HDAC11之概述 19 二、HDAC11與肥胖 20 第四節、山竹子素 (garcinol) 21 一、garcinol 之特性 21 二、garcinol與肥胖 22 第三章、研究目的與實驗架構 23 第一節、研究目的 23 第二節、實驗架構 24 一、動物實驗 24 二、細胞實驗 25 第四章、實驗材料與方法 26 第一節、儀器與材料 26 一、儀器設備 26 二、樣品來源 27 三、藥品與試劑 27 四、分析套組 29 五、抗體 29 六、RT-qPCR 使用之引子 (Primers) 31 第二節、動物實驗方法 31 一、實驗動物來源 31 二、動物飼育管理 31 三、飼料成分與配製 32 四、犧牲程序 33 五、血清生化值測定 34 六、組織切片 34 七、組織蘇木精—伊紅染色 (Hematoxylin and eosin stain, H&E stain) 35 八、組織免疫組織化學染色法 (Immunohistochemistry stain, IHC stain) 37 九、組織均質與蛋白質萃取 39 十、蛋白質定量 40 十一、西方墨點法 (Western blot) 41 十二、糞便 SCFAs 含量測定 44 十三、圖像定量 45 十四、統計分析 46 第三節、細胞實驗方法 47 一、細胞株來源 47 二、細胞培養 47 三、樣品配製 48 四、細胞存活率實驗 (MTT assay) 48 五、細胞誘導分化 49 六、油紅染色 (Oil red O stain) 51 七、細胞蛋白質萃取 51 八、西方墨點法 (western blot) 52 九、mRNA 萃取 52 十、即時定量聚合酶連鎖反應 (RT-qPCR) 53 十一、粒線體質量測定 (mitochondrial mass) 55 十二、圖像定量 56 十三、統計分析 56 第五章、結果與討論 57 第一節、動物實驗結果 57 一、garcinol 對 C57BL/6 小鼠體重之影響 57 二、garcinol 對 C57BL/6 小鼠飲水量及攝食量之影響 59 三、garcinol 對C57BL/6 小鼠血清類升糖素胜肽-1 與瘦素之影響 61 四、garcinol 對 C57BL/6 小鼠臟器重量及肝臟油脂蓄積之影響 65 五、garcinol 對C57BL/6 小鼠肥胖相關血清生化值之影響 68 六、garcinol 對 C57BL/6 小鼠脂肪組織重量與細胞大小之影響 70 七、garcinol 對 C57BL/6 小鼠脂肪組織中脂質代謝之影響 75 八、garcinol 對 C57BL/6 小鼠脂肪組織中 NST 活性之影響 80 九、garcinol 對 C57BL/6 小鼠脂肪組織中 AMPKα 表現量之影響 85 十、garcinol 對 C57BL/6 小鼠脂肪組織中 HDAC11 表現量與反應活性之影響 87 十一、garcinol 對 C57BL/6 小鼠糞便中 SCFAs 之影響 90 第二節、細胞實驗結果 93 一、garcinol 對 3T3-L1 脂肪細胞生存率之影響 93 二、garcinol 對 3T3-L1 脂肪細胞油滴累積之影響 94 三、garcinol 對 3T3-L1 脂肪細胞中脂質代謝之影響 96 四、garcinol 對 3T3-L1 脂肪細胞粒線體生合成之影響 98 五、garcinol 對 3T3-L1 脂肪細胞中 NST 活性之影響 100 六、garcinol 對 3T3-L1 脂肪細胞去乙醯活性與 HDAC11表現之影響 104 第六章、結論 106 參考文獻 109 附錄 121 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 山竹子素 | zh_TW |
| dc.subject | 肥胖 | zh_TW |
| dc.subject | 食慾調控 | zh_TW |
| dc.subject | 短鏈脂肪酸 | zh_TW |
| dc.subject | NST | zh_TW |
| dc.subject | UCP1 | zh_TW |
| dc.subject | HDAC11 | zh_TW |
| dc.subject | obesity | en |
| dc.subject | HDAC11 | en |
| dc.subject | SCFA | en |
| dc.subject | UCP1 | en |
| dc.subject | non-shivering thermogenesis | en |
| dc.subject | appetite-regulating | en |
| dc.subject | garcinol | en |
| dc.title | 山竹子素透過抑制 HDAC11 表現減緩高脂飲食誘導之小鼠肥胖 | zh_TW |
| dc.title | Garcinol alleviates obesity through suppressing HDAC11 expression in high-fat diet-fed mice | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 黃步敏;何元順;洪偉倫 | zh_TW |
| dc.contributor.oralexamcommittee | Bu-Miin Huang;Yuan-Soon Ho;Wei-Lun Hung | en |
| dc.subject.keyword | 山竹子素,肥胖,食慾調控,短鏈脂肪酸,NST,UCP1,HDAC11, | zh_TW |
| dc.subject.keyword | garcinol,obesity,appetite-regulating,non-shivering thermogenesis,UCP1,SCFA,HDAC11, | en |
| dc.relation.page | 124 | - |
| dc.identifier.doi | 10.6342/NTU202402350 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2024-08-10 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 食品科技研究所 | - |
| 顯示於系所單位： | 食品科技研究所 | |
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