請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74911
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 潘敏雄 | |
dc.contributor.author | Wei-Tien Chang | en |
dc.contributor.author | 張瑋恬 | zh_TW |
dc.date.accessioned | 2021-06-17T09:10:07Z | - |
dc.date.available | 2025-03-13 | |
dc.date.copyright | 2020-03-13 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-09-27 | |
dc.identifier.citation | Aguirre, L., Fernandez-Quintela, A., Arias, N., & Portillo, M. P. (2014). Resveratrol: anti-obesity mechanisms of action. Molecules, 19(11), 18632-18655.
Bays, H. E., Gonzalez-Campoy, J. M., Bray, G. A., Kitabchi, A. E., Bergman, D. A., Schorr, A. B., Henry, R. R. (2008). Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther, 6(3), 343-368. Berg, A. H., Combs, T. P., & Scherer, P. E. (2002). ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab, 13(2), 84-89. Bradford, P. G. (2013). Curcumin and obesity. Biofactors, 39(1), 78-87. Choi, S. Y., Hwang, J. H., Ko, H. C., Park, J. G., & Kim, S. J. (2007). Nobiletin from citrus fruit peel inhibits the DNA-binding activity of NF-kappaB and ROS production in LPS-activated RAW 264.7 cells. J Ethnopharmacol, 113(1), 149-155. Choi, Y., Kim, Y., Ham, H., Park, Y., Jeong, H. S., & Lee, J. (2011). Nobiletin suppresses adipogenesis by regulating the expression of adipogenic transcription factors and the activation of AMP-activated protein kinase (AMPK). J Agric Food Chem, 59(24), 12843-12849. de Ferranti, S., & Mozaffarian, D. (2008). The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem, 54(6), 945-955. Farmer, S. R. (2009). Obesity: Be cool, lose weight. Nature, 458(7240), 839-840. Gaidhu, M. P., & Ceddia, R. B. (2011). The role of adenosine monophosphate kinase in remodeling white adipose tissue metabolism. Exerc Sport Sci Rev, 39(2), 102-108. Green, H., & Meuth, M. (1974). An established pre-adipose cell line and its differentiation in culture. Cell, 3(2), 127-133. Gregoire, F. M. (2001). Adipocyte differentiation: from fibroblast to endocrine cell. Exp Biol Med (Maywood), 226(11), 997-1002. Gross, D. N., van den Heuvel, A. P., & Birnbaum, M. J. (2008). The role of FoxO in the regulation of metabolism. Oncogene, 27(16), 2320-2336. Hardie, D. G. (2007). AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol, 8(10), 774-785. Hardie, D. G. (2008). AMPK: a key regulator of energy balance in the single cell and the whole organism. Int J Obes (Lond), 32 Suppl 4, S7-12. Hausman, D. B., DiGirolamo, M., Bartness, T. J., Hausman, G. J., & Martin, R. J. (2001). The biology of white adipocyte proliferation. Obes Rev, 2(4), 239-254. Hawley, S. A., Boudeau, J., Reid, J. L., Mustard, K. J., Udd, L., Makela, T. P., . . . Hardie, D. G. (2003). Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol, 2(4), 28. Hellerstein, M. K. (1999). De novo lipogenesis in humans: metabolic and regulatory aspects. Eur J Clin Nutr, 53 Suppl 1, S53-65. Hirsch, J., & Batchelor, B. (1976). Adipose tissue cellularity in human obesity. Clin Endocrinol Metab, 5(2), 299-311. Jo, J., Gavrilova, O., Pack, S., Jou, W., Mullen, S., Sumner, A. E., . . . Periwal, V. (2009). Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth. PLoS Comput Biol, 5(3), e1000324. Kanda, K., Nishi, K., Kadota, A., Nishimoto, S., Liu, M. C., & Sugahara, T. (2012). Nobiletin suppresses adipocyte differentiation of 3T3-L1 cells by an insulin and IBMX mixture induction. Biochim Biophys Acta, 1820(4), 461-468. Kanneganti, T. D., & Dixit, V. D. (2012). Immunological complications of obesity. Nat Immunol, 13(8), 707-712. Kaul, T. N., Middleton, E., Jr., & Ogra, P. L. (1985). Antiviral effect of flavonoids on human viruses. J Med Virol, 15(1), 71-79. Kim, S., & Moustaid-Moussa, N. (2000). Secretory, endocrine and autocrine/paracrine function of the adipocyte. J Nutr, 130(12), 3110s-3115s. Kurowska, E. M., & Manthey, J. A. (2004). Hypolipidemic effects and absorption of citrus polymethoxylated flavones in hamsters with diet-induced hypercholesterolemia. J Agric Food Chem, 52(10), 2879-2886. Kurowska, E. M., Manthey, J. A., Casaschi, A., & Theriault, A. G. (2004). Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin. Lipids, 39(2), 143-151. Lai, C. S., Li, S., Chai, C. Y., Lo, C. Y., Ho, C. T., Wang, Y. J., & Pan, M. H. (2007). Inhibitory effect of citrus 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone on 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumor promotion in mice. Carcinogenesis, 28(12), 2581-2588. Lane, M. D., & Tang, Q. Q. (2005). From multipotent stem cell to adipocyte. Birth Defects Res A Clin Mol Teratol, 73(7), 476-477. Langin, D. (2006). Control of fatty acid and glycerol release in adipose tissue lipolysis. C R Biol, 329(8), 598-607; discussion 653-595. Leiherer, A., Stoemmer, K., Muendlein, A., Saely, C. H., Kinz, E., Brandtner, E. M., . . . Drexel, H. (2016). Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes. Nutrients, 8(5). Miyata, Y., Sato, T., Imada, K., Dobashi, A., Yano, M., & Ito, A. (2008). A citrus polymethoxyflavonoid, nobiletin, is a novel MEK inhibitor that exhibits antitumor metastasis in human fibrosarcoma HT-1080 cells. Biochem Biophys Res Commun, 366(1), 168-173. Miyata, Y., Tanaka, H., Shimada, A., Sato, T., Ito, A., Yamanouchi, T., & Kosano, H. (2011). Regulation of adipocytokine secretion and adipocyte hypertrophy by polymethoxyflavonoids, nobiletin and tangeretin. Life Sci, 88(13-14), 613-618. Moon, H. S., Chung, C. S., Lee, H. G., Kim, T. G., Choi, Y. J., & Cho, C. S. (2007). Inhibitory effect of (-)-epigallocatechin-3-gallate on lipid accumulation of 3T3-L1 cells. Obesity (Silver Spring), 15(11), 2571-2582. Murakami, A., Nakamura, Y., Torikai, K., Tanaka, T., Koshiba, T., Koshimizu, K., . . . Ohigashi, H. (2000). Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res, 60(18), 5059-5066. Murakami, A., Shigemori, T., & Ohigashi, H. (2005). Zingiberaceous and citrus constituents, 1'-acetoxychavicol acetate, zerumbone, auraptene, and nobiletin, suppress lipopolysaccharide-induced cyclooxygenase-2 expression in RAW264.7 murine macrophages through different modes of action. J Nutr, 135(12 Suppl), 2987s-2992s. Ntambi, J. M., & Young-Cheul, K. (2000). Adipocyte differentiation and gene expression. J Nutr, 130(12), 3122s-3126s. Ouchi, N., Parker, J. L., Lugus, J. J., & Walsh, K. (2011). Adipokines in inflammation and metabolic disease. Nat Rev Immunol, 11(2), 85-97. Reznikoff, C. A., Bertram, J. S., Brankow, D. W., & Heidelberger, C. (1973). Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to postconfluence inhibition of cell division. Cancer Res, 33(12), 3239-3249. Rubin, C. S., Hirsch, A., Fung, C., & Rosen, O. M. (1978). Development of hormone receptors and hormonal responsiveness in vitro. Insulin receptors and insulin sensitivity in the preadipocyte and adipocyte forms of 3T3-L1 cells. J Biol Chem, 253(20), 7570-7578. S., P. E., Metabolic Syndrome-Adipose Tissue. Nature medicine 2014 Sanchez-Delgado, G., Martinez-Tellez, B., Olza, J., Aguilera, C. M., Gil, A., & Ruiz, J. R. (2015). Role of Exercise in the Activation of Brown Adipose Tissue. Ann Nutr Metab, 67(1), 21-32. Smith, P. J., Wise, L. S., Berkowitz, R., Wan, C., & Rubin, C. S. (1988). Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J Biol Chem, 263(19), 9402-9408. Tilg, H., & Moschen, A. R. (2006). Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol, 6(10), 772-783. Trayhurn, P., & Beattie, J. H. (2001). Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc, 60(3), 329-339. Tzeng, S. H., Ko, W. C., Ko, F. N., & Teng, C. M. (1991). Inhibition of platelet aggregation by some flavonoids. Thromb Res, 64(1), 91-100. Vazquez-Vela, M. E., Torres, N., & Tovar, A. R. (2008). White adipose tissue as endocrine organ and its role in obesity. Arch Med Res, 39(8), 715-728. Wang S, Moustaid-Moussa N, Chen L, Mo H, Shastri A, Su S, Bapat P, Kwun IS, Shen CL. (2014) Novel insights of dietary polyphenols and obesity. Journal of Nutritional Biochemistry 25:1-18. Wang, Y., Kim, K. A., Kim, J. H., & Sul, H. S. (2006). Pref-1, a preadipocyte secreted factor that inhibits adipogenesis. J Nutr, 136(12), 2953-2956. Wright, H. M., Clish, C. B., Mikami, T., Hauser, S., Yanagi, K., Hiramatsu, R., . . . Spiegelman, B. M. (2000). A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation. J Biol Chem, 275(3), 1873-1877. Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., . . . Kadowaki, T. (2002). Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med, 8(11), 1288-1295. Yanovski, S. Z., & Yanovski, J. A. (2002). Obesity. N Engl J Med, 346(8), 591-602. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74911 | - |
dc.description.abstract | 隨著社會經濟環境急速變遷與飲食習慣的改變,造成肥胖情形與日俱增 。肥胖將導致罹患許多代謝機能異常疾病的發生,世界衛生組織已將肥胖列為一種慢性疾病且衍生出 〝Globesity〞 (全球肥胖) 一詞,由此可見如何預防肥胖為全世界健康重要課題之一。多甲氧基類黃酮 (Polymethoxyflavones, PMFs) 存在於柑橘類的果皮中,研究發現其具有廣泛的生物活性,如抗發炎、抗癌、抗氧化等功效,目前PMFs抑制脂肪細胞分化的機制尚未清楚,因此本研究以細胞及動物模式探討PMFs抑制脂肪形成的功效和分子機制。細胞實驗加入誘導劑,誘導3T3-L1前脂肪細胞分化,並處理不同含量的PMFs分析其抑制脂肪細胞分化的活性。Oil Red O染色結果顯示PMFs可抑制脂肪細胞油滴的形成。在動物實驗方面,餵食不同含量濃度PMFs-A、B、C可以減少高油脂飲食誘導肥胖小鼠體重以及性腺、腹部脂肪重量的增加,性腺脂肪切片顯示其脂肪細胞大小也有顯著性的縮小,而肝臟切片結果亦可看出脂肪空泡的數量和大小減少;整體又以PMFs-C的效果最為顯著,其次為PMFs-A及PMFs-B。西方墨點法結果顯示PMFs可以透過增加pAMPK的表現量降低脂肪細胞分化轉錄因子C/EBPα和PPARγ減少脂肪酸的形成,進而減少三酸甘油脂的合成。綜合上述結果顯示,PMFs具有抑制脂肪新生作用之功效,並改善高脂飲食誘導之肥胖,能減緩體脂肪生成及脂肪肝的發生,具有開發成不易形成體脂肪的保健食品之潛力,且有趣的是雖然在減少體重上以PMFs-C最為顯著,但在體脂肪率結果顯示不同含量的PMFs皆有顯著減少體脂肪生成之功效。此一發現未來是否可以與現今健康議題;老年人的肌少症做連結,藉由補充不同含量之PMFs達到增加肌肉量、提升代謝能力進而減少體脂肪生成有待更多研究來評估證實。 | zh_TW |
dc.description.abstract | Obesity problems are associate with the rapid changing social and economic environment. Obesity leads to the occurrence of metabolic syndromes. World Health Organization identifies emphasize the important obesity as a chronic disease and the term, ‘Globesity’ the compound word, made of global and obesity , was created. Polymethoxyflavones (PMFs) are found in citrus peel. Some research have suggested that PMFs have anti-inflammatory, anti-cancer, anti-oxidation and other biological activities. However, the inhibitory mechanisms of adipocyte differentiation by PMFs are still unclear. Therefore, this study used in vitro and in vivo models to explore PMFs’ inhibitory effects on the formation of lipid in adipocytes. In the in vitro study, 3T3-L1 preadipocytes were induced inducer mix (DMI) and treated with different compositions of PMFs to evaluate its inhibitory effects on adipocytes differentiation. Results of Oil Red O staining showed that PMFs can inhibit the formation of oil droplets in fat cells. Results of the in vivo study showed that feeding high-fat diet-induced obese mice with different compositions of PMFs-A, B, C reduced their body weight gain, perigonadal fat weight and retroperitoneal fat weight. Gonadal fat biopsy showed a significant decrease in fat cell size, furthermore, histological staining of liver sections showed reduced numbers and sizes of fat vacuoles.;The effect of PMFs-C was the most significant, and PMFs-B effect was greater than PMFs-A. Results of western blot showed that PMFs lowered the fat cell differentiation transcription factor C / EBPα and PPARγ, while increased the amount of pAMPKα, which in turn reduced the synthesis of triglycerides. Based on these results, that PMFs may inhibit hypertrophy in adipocyte, improved high-fat diet-induced obesity and retarded body fat formation and occurrence of fatty liver. Our results showed that PMFs had the potential to be developed into a functional health food that could alleviate the formation of body and liver fats. Interestingly, although PMFs-C were the most significant on weight loss, different compositions of PMFs on body fat ratio results showed significant reductions in body fat production. Whether this finding can be linked to today's health issues or to the myasthenia of the elderly, and by supplementing different compositions of PMFs to increase muscle mass and increase metabolic capacity to reduce body fat production is yet to be confirmed. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T09:10:07Z (GMT). No. of bitstreams: 1 ntu-108-R03641012-1.pdf: 8916361 bytes, checksum: d8c30792e97689be9f31b12e447e04c8 (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 目錄
誌謝I 中文摘要IV AbstractV 目錄VII 附圖目錄X 附表目錄XI 圖目錄XII 表目錄XIII 縮寫表XIV 第一章 緒論 1 第二章 文獻回顧2 第一節、肥胖 (Obesity) 2 (一) 簡介 2 (二) 肥胖定義標準 3 (三) 肥胖的成因 4 (四) 肥胖與疾病 5 (五) 肥胖症的預防及治療 6 第二節、脂肪組織 (Adipocyte tissue) 6 (一) 簡介 6 (二) 脂肪組織的功能與代謝 7 (三) 脂肪組織的內分泌功能 9 第三節、脂肪細胞新生作用 (Adipogenesis) 12 (一) 3T3-L1前脂肪細胞分化 12 (二) 脂肪細胞分化之調控因子 14 第四節、脂肪細胞新生作用過程中訊息傳遞路徑間之調控機制 16 (The regulatory network signaling pathway in adipogenesis) (一) AMPK pathway 在脂肪細胞分化之調控機制 16 第五節、多甲氧基類黃酮 (Polymethoxylflavones ; PMFs) 18 第三章 實驗目的與架構 20 第一節、研究動機與目的 20 第二節、實驗架構 21 第四章 實驗材料與方法 22 第一節、實驗材料 22 (一) 儀器設備 22 (二) 藥品試劑 23 第二節、細胞實驗 (In vitro) 方法 26 (一) 不同含量PMFs 26 (二) 細胞培養 (Cell culutre) 27 (三) 細胞分化 (Adipocyte differentiation) 28 (四) 油紅染色 (Oil red O stain) 29 (五) 細胞存活率試驗 (Trypan blue) 30 (六) 蛋白質萃取 30 (七) 蛋白質定量 31 (八) 西方墨點法 (Western blot) 32 第三節、動物實驗 (In vivo) 方法 35 (一) 實驗動物飼養 35 (二) 高脂飼料配製 36 (三) 實驗動物犧牲 37 (四) 組織包埋與切片 38 第四節、統計分析 41 第五章 結果與討論 42 第一節、細胞實驗 (In vitro) 42 (一) 3T3-L1細胞分化天數之型態觀察 42 (二) 不同含量PMFs抑制3T3-L1脂肪細胞內脂質堆積之情形 43 (三) 不同含量PMFs對3T3-L1脂肪細胞毒性存活率之影響 43 (四) 不同含量PMFs對脂肪細胞分化轉錄因子之蛋白質表現量44 (五) 不同含量PMFs調節AMPK訊息傳遞路徑之蛋白質表現44 第二節、動物實驗 (In vivo)45 (一) 餵食不同含量 PMFs 與 HFD 的動物外觀之差異45 (二) 餵食不同含量 PMFs 與 HFD 的動物體重與攝食量之差異45 (三) 餵食不同含量 PMFs 與 HFD 的動物性腺、腹部、腸繫膜脂肪之差 異46 (四) 餵食不同含量 PMFs 與 HFD 的動物臟器重量之差異47 (五) 餵食不同含量 PMFs 對體脂肪細胞大小之影響48 (六) 餵食不同含量 PMFs 對 HFD 誘導脂肪肝病理狀況之影響48 (七) 血清生化值檢測49 (八) 餵食不同含量 PMFs 調節AMPK訊息傳遞路徑之蛋白質表現50 (九) 餵食不同含量 PMFs 調節脂肪細胞激素Adiponectin蛋白質表現50 第六章 結論51 第七章 圖表52 參考文獻71 附圖目錄 附圖 一、台灣肥胖人口比例 3 附圖 二、肥胖導致相關之疾病 5 附圖 三、脂肪組織 7 附圖 四、脂肪細胞之脂肪生合成作用 9 附圖 五、脂肪細胞之脂解作用 9 附圖 六、脂肪細胞增生與肥大 11 附圖 七、脂肪組織分泌之相關脂肪細胞激素 12 附圖 八、脂肪組織之內分泌功能 12 附圖 九、脂肪細胞的發展 14 附圖 十、脂肪細胞新生作用之過程 14 附圖 十一、脂肪細胞分化之相關轉錄因子 16 附圖 十二、AMPK參與多種器官的能量代謝 18 附圖 十三、 AMPK在脂肪酸再酯化扮演的角色 18 附表目錄 附表 一、成人肥胖標準BMI 4 附表 二、代謝症候群判定標準對照 4 附表 三、橘子皮中鑑定出PMFs與其相關化合物 20 附表 四、Normal diet組成分及熱量表37 附表 五、High-fat diet組成分及熱量表38 圖目錄 Figure 1. Diagram of the compounds in the different chemical compositions of PMFs extracts in citrus peel analyzed using HPLC. . ...55 Figure 2. Morphological changes of the 3T3-L1 preadipocytes treated with DMI. .. 56 Figure 3. Different compositions of PMFs inhibit adipogenesis of 3T3-L1 adipocytes. 57 Figure 4. Effect of different compositions of PMFs on DMI-induced adipogenesis in 3T3-L1 preadipocytes cell viability. 58 Figure 5. Effects of different compositions of PMFs on C/EBPα and PPARγ protein expressions in 3T3-L1 adipocyte. 59 Figure 6. Effects of different compositions of PMFs on activation AMPK signaling in 3T3-L1 adipocyte. 60 Figure 7. Effect of different compositions of PMFs on HFD-induced obesity in C57BL/6 mice. 61 Figure 8. Effect of supplement with different compositions of PMFs on body weight and in HFD fed C57BL/6 mice for 16 weeks . 62 Figure 9. Effect of different compositions of PMFs on relative white adipocyte tissue weights in HFD-induced obesity in C57BL/6 mice. 63 Figure 10. Effect of different compositions of PMFs on white adipocyte tissue weight percentage of body weights. 64 Figure 11. Effect of different compositions of PMFs on adipocyte size. 65 Figure 12. Changes in liver histological stained with H&E in different compositions of PMFs supplement in HFD-feeding mice. 66 Figure 13. Effects of different compositions of PMFs on activation AMPK signaling in adipose tissue in HFD-fed C57BL/6 mice. 67 Figure 14. Effects of different compositions of PMFs on Adiponectin protein expressions in adipose tissue in HFD-fed C57BL/6 mice. 68 Figure 15. Different chemical compositions of polymethoxyflavones (PMFs) inhibit adipogenesis in 3T3-L1 preadipocytes and suppress obesity in high-fat diet-feeding C57BL/6 mice.68 表目錄 Table 1. The composition and contents of PMF in orange peel extract 70 Table 2. Effect of HFD and supplement of different compositions of PMFs on organ weight in C57BL/6 mice 71 Table 3. Effect of different compositions of PMFs on serum biochemical parameters 72 | |
dc.language.iso | zh-TW | |
dc.title | 不同化學組成含量之多甲氧基類黃酮抑制脂肪細胞
新生及減緩高脂飲食誘導小鼠之肥胖 | zh_TW |
dc.title | Different chemical compositions of polymethoxyflavones (PMFs)
inhibit adipogenesis in 3T3-L1 preadipocytes and suppress obesity in high-fat diet-feeding C57BL/6 mice | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 何其儻,王應然,何元順,魏宗德 | |
dc.subject.keyword | 肥胖,脂肪細胞新生作用,多甲氧基類黃酮 (PMFs),高脂飲食, | zh_TW |
dc.subject.keyword | Obesity,Adipogenesis,Polymethoxyflavones (PMFs),High-fat diet, | en |
dc.relation.page | 76 | |
dc.identifier.doi | 10.6342/NTU201904161 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2019-10-01 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 食品科技研究所 | zh_TW |
顯示於系所單位: | 食品科技研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-108-1.pdf 目前未授權公開取用 | 8.71 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。