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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃青真 | |
| dc.contributor.author | Shang-Yu Zou | en |
| dc.contributor.author | 鄒尚瑀 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:45:12Z | - |
| dc.date.available | 2021-08-31 | |
| dc.date.copyright | 2016-08-31 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-12 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49738 | - |
| dc.description.abstract | 肥胖起因於長期能量攝取大於消耗，體內累積過多脂肪。而肥胖患者中，又以腹部肥胖者有較高機率罹患糖尿病、高血脂症及心血管疾病。代謝症候群指高血壓、高血糖、腹部肥胖與血脂異常等症狀至少三項存在者，未經適當控制則有極高風險轉為第二型糖尿病及心血管疾病。目前許多研究證實苦瓜具有抗肥胖及改善代謝異常之潛力。本實驗室發現餵食C57BL/6J小鼠山苦瓜全果凍乾粉之高糖飲食25週後，能促進白色脂肪褐化相關基因表現。目前研究認為，白色脂肪褐化可增加個體熱量消耗，對抗肥胖。苦瓜具有多項生理活性，其中所含之三萜類化合物具有血糖調節能力，並以不帶醣基之形式調節效果較佳。過去於3T3-L1脂肪細胞模式中，發現山苦瓜酸水解產物之正己烷萃物能改變促褐化效果。本論文旨在探討山苦瓜及其水解產物，改善高脂飲食誘發肥胖小鼠之代謝異常及促進脂肪褐化之效果。
本實驗以高脂飲食誘發C57BL/6J小鼠肥胖15週，再分5組分別餵食高脂飼料 (HF組)、高脂飼料添加3%山苦瓜粉 (3%BGP組)、高脂飼料添加3%水解山苦瓜粉 (3%BGPa組)、高脂飼料添加5%山苦瓜粉 (5%BGP組) 及高脂飼料添加5%水解山苦瓜粉 (5%BGPa組) 餵食20週，另以飼養期間全程餵食chow diet之C組作為正常對照組。結果顯示，短期 (11週) 攝入3%水解山苦瓜及5%山苦瓜及其水解產物可有效降低血糖; 長期 (20週) 攝入則有降低體重增加之效果。短期及長期攝入3%及5%山苦瓜及其水解產物皆可有效降低血清中總膽固醇。進一步分析 脂肪基因表現，5%山苦瓜可促進棕色脂肪組織 (BAT) 中產熱功能及粒線體生合成基因表現，並增加腎周圍脂肪 (RWAT) 中生熱及粒線體生合成基因表現。5%水解山苦瓜則可促進副睪脂肪組織 (EWAT) 褐化指標及粒線體生合成基因表現。綜合以上，山苦瓜及其水解產物能促進棕色脂肪產熱功能及白色脂肪褐化基因之表現，並降低血清總膽固醇及增加胰島素敏感度，改善小鼠肥胖及代謝異常情形。 | zh_TW |
| dc.description.abstract | Obesity is defined as abnormal or excessive body fat accumulation due to excessive energy intake and less energy expenditure. Abdominal obesity is a risk factor for metabolic disorder related to diabetes, hyperlipidemia and cardiovascular diseases. Metabolic syndrome is the clustering of various risk factors those predictive higher risks of type 2 diabetes and cardiovascular diseases. Numerous studies have demonstrated that bitter melon (Momordica charantisa) has potential for ameliorating obesity and metabolic syndrome. Previous studies showed that mice fed high sucrose diet supplemented with bitter gourd powder (BGP) for 25 weeks had higher mRNA expression of genes related to browning in white adipose tissue, which is considered an effective way to increase energy expenditure and combat obesity. Bitter melon is known to have a number of health benefits. For instance, the triterpenoids in bitter melon, especially aglycone forms, have been shown to activate AMPK and increase glucose uptake in adipocytes and myocytes. It has been demonstrated the hexane extracts of acid-hydrolyzed BGP has been shown to induce “browning” related mRNA expressions in the 3T3-L1-cell model. In this study, we aimed to examine the effects of BGP and its hydrolysis product on ameliorating metabolic disorders and stimulating adipose tissue browning of high fat diet induced obese mice.
C57BL/6J mice were fed the high fat diet for 15 weeks and then assigned into 5 groups, including: HF group (fed the high fat diet), 3%BGP group (fed the high fat diet supplemented with 3%BGP), 3%BGPa group (fed the high fat diet supplemented with 3% hydrolyzed BGP), 5%BGP group (fed the high fat diet supplemented with 5%BGP), and 5%BGPa group (fed the high fat diet supplemented with 5% hydrolyzed BGP). They were fed the respective test diets for 20 week. Another group of mice fed a chow diet throughout the 35 weeks periods served as the normal control. Compared to the HF group, mice in the 3%BGPa, 5%BGP and 5%BGPa groups had significantly lower serum glucose at 11 weeks, and significantly lower body weight gain after 20 weeks. Serum cholesterol level of 3%BGP, 3%BGPa, 5%BGP and 5%BGPa groups were significantly lower than those of the HF group at 11 and 20 week. The mRNA expressions of thermogenic and mitochondrial biogenic genes in BAT and RWAT of the 5%BGP were significantly higher than the HF group. In addition, mice fed the 5%BGPa diet showed significantly higher mRNA expression of beige markers and mitochondrial biogenic genes in EWAT. In conclusion, BGP and hydrolyzed BGP up-regulated the expression of thermogenic genes in BAT and brown-related genes in visceral white adipose tissue, reduced serum cholesterol and increased insulin sensitivity. Results of this study support the effects of BGP and its hydrolysis product on ameliorating the diet-induced obesity and metabolic disorder, and presumably can promote browning in mice. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:45:12Z (GMT). No. of bitstreams: 1 ntu-105-R03b22002-1.pdf: 14460398 bytes, checksum: f18f6880f54f6a913950a7a94c577937 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 總目錄
中文摘要 I Abstact III 縮寫對照表 V 第一章 緒論 1 第一節 前言 1 第二節 文獻回顧 3 一、肥胖 3 二、代謝症候群與第二型糖尿病 3 三、過氧化體增殖劑活化受體 5 3.1 PPARs異形體 (isoform) 5 3.2 PPARs之ligands與agonists 6 3.3 PPARγ於脂肪組織之作用 6 四、粒線體 8 4.1 粒線體生合成與相關調控基因 8 4.2 粒線體之融合與分裂 10 4.3 粒線體功能缺失與代謝疾病 11 4.4 棕色脂肪組織中的粒線體 11 4.5 白色脂肪組織中的粒線體 12 五、脂肪組織與褐化現象 13 5.1 脂肪組織 13 5.2 白色脂肪褐化機制 (browning) 14 5.3 脂肪褐化常伴隨表現量提高之粒線體功能及生熱等相關基因 15 六、山苦瓜 19 6.1 自苦瓜分離之化合物 19 6.2 苦瓜與代謝症候群 20 6.3 苦瓜與白色脂肪褐化 21 第三節 實驗假說與架構 22 一、實驗假說 22 二、實驗架構 23 第二章 實驗設計與材料方法 24 第一節 實驗設計 24 第二節 材料方法 25 一、動物飼養 25 二、飼料 25 2.1 山苦瓜樣品 25 2.2 山苦瓜水解粉末 25 2.3 高脂飼料及添加BGP、BGPa高脂飼料 26 2.4 chow diet 26 三、氧消耗量、二氧化碳排出量及呼吸商測定 (Indirect calorimetry study) 29 四、禁食血清樣本收集 29 五、動物犧牲 29 六、血糖分析 30 七、血清胰島素分析 30 7.1 市售試劑組 (Mouse insulin ELISA, Mercodia) 30 7.2 實驗方法 31 7.3 胰島素阻抗指標 (HOMA-IR index) 31 八、血清中脂質分析 31 8.1 血清中三酸甘油酯測定 31 8.2 血清中膽固醇測定 32 九、脂肪組織切片觀察及細胞面積定量 33 十、組織基因mRNA表現分析 33 10.1 組織總RNA抽取 33 10.2 總RNA反轉錄成cDNA 34 10.3 Quantitative Real-time PCR 34 十一、統計分析 35 第三章 實驗結果 37 第一節 生長情形 37 一、體重變化、攝食量與飼料利用率 37 二、器官及組織之絕對與相對重量 38 2.1 絕對重量 38 2.2 相對重量 38 三、氧氣消耗量、二氧化碳排出量與呼吸商分析 39 3.1 氧氣消耗量 39 3.2 二氧化碳排出量 39 3.3 呼吸商 39 第二節 血清生化分析 40 一、血糖 40 二、血清胰島素與胰島素阻抗指標 40 三、血清三酸甘油酯 40 四、血清總膽固醇 41 第三節 脂肪組織型態觀察 41 一、BAT切片H&E染色結果 41 二、IWAT切片H&E染色及細胞面積定量結果 41 三、EWAT切片H&E染色及細胞面積定量結果 42 四、RWAT切片H&E染色及細胞面積定量結果 42 第四節 脂肪組織褐化相關基因表現 42 一、BAT生熱及粒線體生合成相關基因mRNA表現 42 二、IWAT褐化相關基因mRNA表現 43 三、EWAT褐化相關基因mRNA表現 43 四、RWAT褐化相關基因mRNA表現 44 第四章 討論 67 第一節 山苦瓜改善小鼠代謝異常 67 一、山苦瓜暨其水解產物對小鼠生長情形、飼料利用率之影響 67 二、山苦瓜暨其水解產物對小鼠新陳代謝之影響 68 三、山苦瓜暨其水解產物能調節血糖、血清總膽固醇及改善胰島素敏感度 69 第二節 山苦瓜能促進BAT產熱功能及粒線體生合成相關基因表現 70 第三節 山苦瓜無法促進皮下脂肪中生熱及粒線體生合成相關基因表現 71 第四節 山苦瓜能促進內臟脂肪中生熱及粒線體生合成相關基因表現 72 一、山苦瓜水解產物能促進EWAT褐化指標及粒線體生合成相關基因表現 72 二、山苦瓜能促進RWAT中生熱及粒線體生合成相關基因表現 72 第五節 比較水解前後山苦瓜對小鼠代謝情形及白脂褐化之影響 74 第五章 結論 81 第六章 參考文獻 89 圖目錄 圖1-1 PPARs核受器結構 5 圖1-2 PPARγ對脂肪組織調控扮演多重角色 7 圖1-3粒線體生合成機制 9 圖1-4粒線體生命週期與型態變化及自噬調控 10 圖1-5 棕色脂肪細胞能量利用機制 12 圖1-6 脂肪組織褐化調控及受環境影響之可逆現象 15 圖1-7 UCP1受β3-adrenergic receptor (β3-AR) 活化示意圖 16 圖1-8 Catecholamine及natriuretic誘發生熱作用 18 圖3-1 C57BL/6J小鼠肥胖誘導15週及正式實驗19週期間之生長曲線 45 圖3-2 C57BL/6J小鼠正式實驗期間之各週平均每日(A)攝食量與(B)能量攝取 46 圖3-3 C57BL/6J小鼠正式實驗第14-18週之 (A)氧氣消耗量與 (B)曲線下面積 51 圖3-4 C57BL/6J小鼠正式實驗第14-18週之 (A)平均二氧化碳排出量與 (B)曲線下面積 52 圖3-5 C57BL/6J小鼠正式實驗第第14-18週之 (A)呼吸商及 (B)曲線下面積與 (C)平均呼吸商 53 圖3-6 C57BL/6J小鼠苦瓜分組前之-1週及正式實驗第11週與第20週之血清 (A)葡萄糖、(B)TG及 (C)總膽固醇 55 圖3-7 C57BL/6J小鼠體重與血清 (A)葡萄糖、(B)TG及 (C)膽固醇相關性 56 圖3-8 C57BL/6J小鼠正式實驗第20週之胰島素阻抗指標 57 圖3-9 C57BL/6J小鼠正式實驗第20週之棕色脂肪組織切片H&E染色 58 圖3-10 C57BL/6J小鼠正式實驗第20週之鼠蹊部白色脂肪組織切片H&E染色 59 圖3-11 C57BL/6J小鼠正式實驗第20週之副睪白色脂肪組織切片H&E染色 60 圖3-12 C57BL/6J小鼠正式實驗第20週之腎周圍白色脂肪組織切片H&E染色 61 圖3-13 C57BL/6J小鼠 (A) BAT油滴大小與 (B) IWAT、(C) EWAT及(D) RWAT脂肪細胞平均面積 62 圖3-14 C57BL/6J小鼠正式實驗第20週之棕色脂肪基因mRNA表現 63 圖3-15 C57BL/6J小鼠正式實驗第20週之鼠蹊部白色脂肪基因mRNA表現 64 圖3-16 C57BL/6J小鼠正式實驗第20週之副睪白色脂肪基因mRNA表現 65 圖4-1 C57BL/6J小鼠各組之IWAT、EWAT及RWAT脂肪細胞平均面積與血清胰島素及胰島素阻抗指標相關性………………………………………………………………………..77 表目錄 表2-1 HF diet及添加山苦瓜粉之飼料配方 27 表2-2 Chow diet飼料配方 28 表2-3 qPCR分析使用引子整理表 36 表3-1 C57BL/6J小鼠正式實驗19週期間之初始體重、終體重與體重增加量....................47 表3-2 C57BL/6J小鼠正式實驗19週期間之攝食量、能量攝取、攝食與能量利用率 48 表3-3 C57BL/6J小鼠正式實驗第20週之體重及臟器絕對重量 49 表3-4 C57BL/6J小鼠正式實驗第20週之臟器相對重量 50 表3-5 C57BL/6J小鼠苦瓜分組前之-1週及正式實驗第11週與第20週之血糖、血清TG及血清總膽固醇 54 表3-6 C57BL/6J小鼠正式實驗第20週之血清胰島素 57 表4-1本實驗室過去研究與本研究結果比較…………………………………………………78 表4-2本實驗室過去研究與本研究之山苦瓜影響脂肪組織mRNA表現量整理 79 表4-3本實驗室過去研究與本研究之山苦瓜影響脂肪組織mRNA表現量整理 80 表5-1 C57BL/6J小鼠正式實驗期間各組每週平均體重及two-way ANOVA統計結果整理 …..................................................................................................................................................83 表5-2 C57BL/6J小鼠正式實驗週期間之體重增加量、飼料利用率、血清生化分析及胰島素阻抗指標two-way ANOVA統計結果整理 84 表5-3 C57BL/6J小鼠正式實驗第20週之BAT mRNA表現two-way ANOVA統計結果整理 85 表5-4 C57BL/6J小鼠正式實驗第20週之IWAT mRNA表現two-way ANOVA統計結果整理 86 表5-5 C57BL/6J小鼠正式實驗第20週之EWAT mRNA表現two-way ANOVA統計結果整理 87 表5-6 C57BL/6J小鼠正式實驗第20 週之RWAT mRNA表現two-way ANOVA統計結果整理 88 | |
| dc.language.iso | zh-TW | |
| dc.subject | 水解 | zh_TW |
| dc.subject | 肥胖 | zh_TW |
| dc.subject | 山苦瓜 | zh_TW |
| dc.subject | 褐化 | zh_TW |
| dc.subject | 粒線體 | zh_TW |
| dc.subject | 三?類化合物 | zh_TW |
| dc.subject | hydrolysis | en |
| dc.subject | obesity | en |
| dc.subject | bitter melon | en |
| dc.subject | browning | en |
| dc.subject | mitochondria | en |
| dc.subject | triterpenoids | en |
| dc.title | 長期餵食山苦瓜對高脂飲食誘導肥胖小鼠代謝異常及白色脂肪組織褐化相關基因表現之效應 | zh_TW |
| dc.title | The Effects of Wild Bitter Gourd on High-Fat Diet Induced
Metabolic Disorder and the Expression of Browning-Related Genes in White Adipose Tissue of C57BL/6J Mice | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 呂紹俊,張美鈴,林甫容,蘇慧敏 | |
| dc.subject.keyword | 肥胖,山苦瓜,褐化,粒線體,三?類化合物,水解, | zh_TW |
| dc.subject.keyword | obesity,bitter melon,browning,mitochondria,triterpenoids,hydrolysis, | en |
| dc.relation.page | 103 | |
| dc.identifier.doi | 10.6342/NTU201602470 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-15 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-105-1.pdf 未授權公開取用 | 14.12 MB | Adobe PDF |
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