(18.207.253.100) 您好!臺灣時間:2021/05/06 08:03
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:韓欣穎
研究生(外文):Hsin-Ying Han
論文名稱:天然物之抗肥胖藥效研究:針對脂肪細胞生命週期進行藥物機制探討
論文名稱(外文):Anti-obesity with phytochemicals: targeting adipocyte life cycle and mechanism studies
指導教授:沈家寧劉慧康
指導教授(外文):Chia-Ning ShenHui-Kang Liu
學位類別:碩士
校院名稱:國立臺灣海洋大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:79
中文關鍵詞:抗肥胖12346-O-五没食子酰葡萄糖脂肪前驅細胞脂肪細胞細胞凋亡胰島素
外文關鍵詞:Anti-obesity1, 2, 3, 4, 6-penta-O-galloyl-(α /β)PreadipocyteAdipocyteApoptosisInsulin
相關次數:
  • 被引用被引用:1
  • 點閱點閱:368
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:36
  • 收藏至我的研究室書目清單書目收藏:0
肥胖患者之脂肪組織特色在於細胞轉換速率變快及成熟的脂肪細胞肥大,因此可藉由調控脂肪細胞的生成過程,例如:從抑制脂肪前驅細胞的增生、阻斷脂肪前驅細胞分化成為脂肪細胞、促進脂肪細胞之脂肪分解或是誘發走向細胞凋亡途徑等達到因減少細胞數量及體積而產生減肥的效果。由Guy Kleins’ ( 2007 ) 文獻中指出大花紫薇具有抗肥胖以及抗糖尿病的功效。本研究採用藥物為大花紫薇中天然成分β-PGG及其異構物α-PGG,比較對於脂肪細胞生命周期進行干預的活性及可能的機轉探討。實驗證實PGGs皆具有類似胰島素的作用。不過兩種化合物對脂肪前驅細胞促進細胞凋亡,進而達到減少分化之脂肪細胞數量的活性並無法透過抑制胰島素受體所避免。此外兩種化合物皆具有抑制脂肪前驅細胞分化後之三酸甘油脂堆積及甘油釋出,perilipin的表現量受到藥物處理所造成的抑制效果暗示細胞中的油滴形成機制應受到破壞。對已分化之脂肪細胞來說,-PGG不同於β-PGG,可促進兩倍的甘油釋出卻沒有伴隨游離脂肪酸的釋出增加,機轉有待進一步探討。總結本研究,結果證實α-PGG和β-PGG具有干預脂肪細胞生命周期的活性,因此有作為減肥藥的發展潛力。
In terms of obesity, increased fat mass, fat cell turnover rate, and fat cell hypertrophy commonly occur in obese subjects. Therefore, reducing preadipocyte cell numbers, blocking preadipocyte differentiation, and promoting lipolysis or apoptosis of adipocytes could lead to anti-obesity effects. Based on Guy Kleins’ work, Lagerstroemia speciosa have both anti-diabetes and obesity activity. Therefore, current investigation employed the active principle, 1, 2, 3, 4, 6-penta-O-galloyl-
-D-glucose (-PGG), identified from Lagerstroemia speciosa and its isoform to compare the impact of both agents on the various stages of adipocyte life cycle. As a result, in 3T3L-1 preadipocytes, both compounds could promote apoptosis and reduce the number of preadipocytes for later differentiation in insulin-receptor independent manner. In addition, the presence of PGGs could intervene 3T3-L1 adipogenic process judging by the level of lipid content and glycerol release at the end of differentiation. The formation of lipid droplet appeared to be affected by reducing perilipin protein expression after PGGs treatment. Different from -PGG, -PGG could promote 2-fold glycerol release in adipocytes without increasing free fatty acids. The possible mechanisms remained to be elucidated. In conclusion, current investigation suggested that both PGGs have potential to be developed as anti-obesity agents via targeting adipocyte life cycle.

中文摘要 2
Abstract 3
圖目錄 5
中英文對照表 8
英文縮寫對照表 10
前言 11
2. 脂肪組織 12
2.1 脂肪組織的基本功能 12
2.2 脂肪的生成與代謝 13
2.2.1脂質代謝調控 13
2.2.2甘油新生 14
3. 胰島素調控生理代謝機制 15
3.2. 胰島素對脂肪細胞的調控 16
4. 脂肪細胞 17
4.1 脂肪細胞的發育及生命周期 17
4.2 脂肪細胞的分化機制 18
4.3 脂肪細胞的自我調控與肥胖關係 19
5. 細胞凋亡 20
6. 市面上常見減肥藥評比 21
7. Penta-O-galloyl-D-glucopyranose (PGG) 23
8. 研究動機 24
材料與方法 25
1 材料 25
1.1藥品 25
1.2儀器 26
2 方法 26
2.1 細胞培養 (cell culture) 26
a.3T3-L1纖維母細胞 (Fibroblast) 26
b.H4IIE-C3 (liver cell ) 27
2.2 細胞分化 27
2.3 Oil Red O 染色 ( Oil Red O stain ) 28
2.4 甘油含量測定( Glycerol determination )28
2.5 MTT細胞存活率實驗 ( MTT assay ) 28
2.6 西方點墨法 ( Western blot ) 29
2.7 細胞週期分析 31
2.8 細胞凋亡分析 31
2.9 反轉錄聚合酶鏈鎖反應 ( RT-PCR ) 32
2.10 自由脂肪酸測定 33
2.11 統計分析 34
結果 35
1. α-PGG與β-PGG對於抑制肝臟細胞(H4IIE)的PEPCK mRNA表現量的活性比較及長時間重覆給藥處理對肝臟細胞(H4IIE)的細胞存活率影響 35
2. α-PGG與β-PGG長時間重覆給藥處理對間質幹細胞的細胞存活率在不同濃度下的影響。 36
3. α-PGG與β-PGG短時間與長時間重覆給藥處理對3T3-L1脂肪前驅細胞的細胞存活率在不同濃度下影響。 36
4.α-PGG與β-PGG長時間重覆給藥處理對3T3-L1脂肪前驅細胞的細胞週期影響。 37
5. 3T3-L1脂肪前驅細胞在給予α-PGG與β-PGG於高濃度下 72 37
小時與於低濃度連續處理下6天後的細胞凋亡或壞死比例變化 37
6. 3T3-L1脂肪前驅細胞在給予α-PGG與β-PGG重覆加藥處理下6天後的細胞凋亡訊息傳遞現象。 38
7. α-PGG與β-PGG在長時間重覆給藥處理對3T3-L1脂肪前驅細胞的細胞存活率在加入胰島素抑制劑下的影響。 39
8. 誘導3T3-L1脂肪前驅細胞時重覆加入α-PGG與β-PGG下對於脂肪細胞分化的效果。 40
9. 誘導3T3-L1脂肪前驅細胞時重覆加入α-PGG與β-PGG對於分化過程結束後之脂肪細胞三酸甘油脂堆積與甘油釋出的效果。 40
10. α-PGG與β-PGG短時間與長時間重覆加藥處理對3T3-L1脂肪細胞的細胞存活率在不同濃度下影響。 41
11. α-PGG與β-PGG長時間處理影響脂肪細胞的三酸甘油脂堆積、甘油釋出與脂肪酸釋出比較。 42
討論 43
參考文獻: 48


參考文獻:
行政院衛生署統計公布欄http://www.doh.gov.tw/CHT2006/DM/DM2.
http://www.cellsignal.com/pdf/9930.pdf.

BAI, N., KAN HE, MARC ROLLER, BOLIN ZHENG, XIAOZHUO CHEN, ZHONGGUANG SHAO, & TANGSHENG PENG, A.Q.Z. (2008) Active Compounds from Lagerstroemia speciosa, Insulin-like Glucose Uptake-Stimulatory/Inhibitory and Adipocyte Differentiation-Inhibitory Activities in 3T3-L1 Cells. Agricultural and food chemistry, 56.

Bunnell, B.A., Flaat, M., Gagliardi, C., Patel, B., & Ripoll, C. (2008) Adipose-derived stem cells: isolation, expansion and differentiation. Methods, 45, 115-20.

Dahlman, I. & Arner, P. (2007) Obesity and polymorphisms in genes regulating human adipose tissue. Int J Obes (Lond), 31, 1629-41.

Danial, N.N. & Korsmeyer, S.J. (2004) Cell death: critical control points. Cell, 116, 205-19.

Forest, C., Tordjman, J., Glorian, M., Duplus, E., Chauvet, G., Quette, J., Beale, E.G., & Antoine, B. (2003) Fatty acid recycling in adipocytes: a role for glyceroneogenesis and phosphoenolpyruvate carboxykinase. Biochem Soc Trans, 31, 1125-9.

Guilherme, A., Virbasius, J.V., Puri, V., & Czech, M.P. (2008) Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol, 9, 367-77.

Hwang, J.T., Kim, S.H., Lee, M.S., Kim, S.H., Yang, H.J., Kim, M.J., Kim, H.S., Ha, J., Kim, M.S., & Kwon, D.Y. (2007) Anti-obesity effects of ginsenoside Rh2 are associated with the activation of AMPK signaling pathway in 3T3-L1 adipocyte. Biochem Biophys Res Commun, 364, 1002-8.

Klein, G., Kim, J., Himmeldirk, K., Cao, Y., & Chen, X. (2007) Antidiabetes and Anti-obesity Activity of Lagerstroemia speciosa. eCAM, 13, 1-7.

Langin, D. (2006) Control of fatty acid and glycerol release in adipose tissue lipolysis. C R Biol, 329, 598-607; discussion 653-5.
Lefterova, M.I. & Lazar, M.A. (2009) New developments in adipogenesis. Trends Endocrinol Metab, 20, 107-14.
Li, Y., Kim, J., Li, J., Liu, F., Liu, X., Himmeldirk, K., Ren, Y., Wagner, T.E., & Chen, X. (2005) Natural anti-diabetic compound 1,2,3,4,6-penta-O-galloyl-D-glucopyranose binds to insulin receptor and activates insulin-mediated glucose transport signaling pathway. Biochemical and Biophysical Research Communications, 336, 430-437.

Lin, J., Della-Fera, M.A., & Baile, C.A. (2005) Green tea polyphenol epigallocatechin gallate inhibits adipogenesis and induces apoptosis in 3T3-L1 adipocytes. Obes Res, 13, 982-90.

Liu, H.K., Green, B.D., McClenaghan, N.H., McCluskey, J.T., & Flatt, P.R. (2004) Long-term beneficial effects of vanadate, tungstate, and molybdate on insulin secretion and function of cultured beta cells. Pancreas, 28, 364-8.

Liu, X., Kim, J.K., Li, Y., Li, J., Liu, F., & Chen, X. (2005) Tannic acid stimulates glucose transport and inhibits adipocyte differentiation in 3T3-L1 cells. J Nutr, 135, 165-71.

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, 2571-82.

Ntambi, J.M. & Young-Cheul, K. (2000) Adipocyte differentiation and gene expression. J Nutr, 130, 3122S-3126S.

Nye, C., Kim, J., Kalhan, S.C., & Hanson, R.W. (2008a) Reassessing triglyceride synthesis in adipose tissue. Trends Endocrinol Metab, 19, 356-61.

Nye, C.K., Hanson, R.W., & Kalhan, S.C. (2008b) Glyceroneogenesis is the dominant pathway for triglyceride glycerol synthesis in vivo in the rat. J Biol Chem, 283, 27565-74.

Park, B.H., Qiang, L., & Farmer, S.R. (2004) Phosphorylation of C/EBPbeta at a consensus extracellular signal-regulated kinase/glycogen synthase kinase 3 site is required for the induction of adiponectin gene expression during the differentiation of mouse fibroblasts into adipocytes. Mol Cell Biol, 24, 8671-80.

Pirola, L., Johnston, A.M., & Van Obberghen, E. (2004) Modulation of insulin action. Diabetologia, 47, 170-84.

Prusty, D., Park, B.H., Davis, K.E., & Farmer, S.R. (2002) Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma ) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes. J Biol Chem, 277, 46226-32.

Rayalam, S., Della-Fera, M.A., & Baile, C.A. (2008) Phytochemicals and regulation of the adipocyte life cycle. J Nutr Biochem, 19, 717-26.

Reshef, L., Olswang, Y., Cassuto, H., Blum, B., Croniger, C.M., Kalhan, S.C., Tilghman, S.M., & Hanson, R.W. (2003) Glyceroneogenesis and the triglyceride/fatty acid cycle. J Biol Chem, 278, 30413-6.

Student, A.K., Hsu, R.Y., & Lane, M.D. (1980) Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes. J Biol Chem, 255, 4745-50.

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, 715-28.

Yang, X., Lu, X., Lombes, M., Rha, G.B., Chi, Y.I., Guerin, T.M., Smart, E.J., & Liu, J. The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab, 11, 194-205.

Zhang, J., Li, L., Kim, S.H., Hagerman, A.E., & Lu, J. (2009) Anti-cancer, anti-diabetic and other pharmacologic and biological activities of penta-galloyl-glucose. Pharm Res, 26, 2066-80.



連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔