题名

探討台灣藜外殼萃出物對3T3-L1脂肪前驅細胞分化之影響

并列篇名

Effects of Chenopodium fromosanum Koidz. Husk Extracts on 3T3-L1 preadipocytes differentiation

DOI

10.6840/cycu201700826

作者

李柔萱

关键词

肥胖 ; 台灣藜 ; 3T3-L1脂肪前驅細胞 ; Obesity ; Chenopodium formosanum Koidz ; 3T3-L1 preadipocytes

期刊名称

中原大學生物科技學系學位論文

卷期/出版年月

2017年

学位类别

碩士

导师

吳亮宜

内容语文

繁體中文

中文摘要

肥胖起因於能量攝取與代謝消耗之不平衡,而導致脂肪細胞數目增加並肥大,是在現今社會中常見的一種代謝疾病,其不但會造成生活上的不便,更會增加罹患其他疾病,如高血壓、第二型糖尿病、癌症等等之風險。因此本實驗期許能找出具有特殊生理功能的食材,望能開發出具有預防肥胖功能之保健食材。 台灣藜 (Chenopodium formosanum Koidz) 為台灣特有原生作物,其具有較其他穀類作物更高量的營養價值及優質的機能性成分,包括皂素、甜菜色素、綠原酸及膳食纖維等。而過去研究指出,台灣藜大部分的機能性成分皆在外殼。因此本實驗以台灣藜外殼為主要材料,經水、甲醇和乙醇萃取後,製成台灣藜殼之不同溶劑萃取物,並進行對3T3-L1脂肪前驅細胞之毒性,接著探討這些萃出物對3T3-L1脂肪前驅細胞分化之影響,進一步針對效果最顯著之萃取物進行影響機制的探討。 實驗結果顯示台灣藜外殼水萃物可以抑制脂肪細胞油滴生成之情形,具有減少脂肪細胞分化之結果。而甲醇及乙醇萃出物則不具影響3T3-L1脂肪前驅細胞分化之效果。另外我們也發現台灣藜外殼水萃物是藉由增加分化期初期Pref-1的表現量,進而降低脂肪生成過程中之脂肪細胞分化相關轉錄因子C/EBPα、PPARγ的表現;同時也降低分化中ERK蛋白質磷酸化的現象,最終降低脂肪細胞油滴的生成。結果顯示台灣藜殼萃出物具有抑制脂肪細胞分化之功效,推測其具有抗肥胖之潛力。

英文摘要

Obesity because of an imbalance in energy intake and expenditure leads to increased fat cells number and increased fat cells size. Obesity is a common metabolism diseases and not only inconvenient but also risk factor for other diseases including hypertension, type 2 diabetes, cancer, and so on. This study expected to find that have some physiological function in food and make the health food that can prevention obesity. Djulis (Chenopodium formosanum Koidz) is a Taiwanese cereal plant, rich in nutritive and high quality functional compounds, contain betalain, chlorogenic acid and dietary fiber. Previous studies said the most function composition on husk. This study get on MTT assay by Djulis husk water extracts (DHWE), Djulis husk methanol extracts (DHME) and Djulis husk ethanol extracts (DHEE). Then to find the effect of these extracts on 3T3-L1 preadipocytes differentiation and to find the pathway. In result, DHWE inhibited on adipocyte differentiation but not impact on DHME or DHEE. Morever we found that DHWE can add expressions of Pref-1 (Preadipocyte factor 1) , and reduced the expression of C/EBPα (CCAAT/enhancer binding protein alpha) and PPARγ (Peroxisome proliferator-activated receptor gamma) . At the same time DHWE reduced the phosphorylation on extracellular Signal-Regulated Kinase (ERK) in cells. Simultaneously, inhibited generation of oil droplets by reduced the expressions The results suggested that DHWE can delay the 3T3-L1 preadipocytes differentiation cycle and it is possible having potential on anti-obesity.

主题分类 理學院 > 生物科技學系
生物農學 > 生物科學
参考文献
  1. 潘文涵, 吳幸娟, 葉志嶸, 莊紹源, 張新儀, 葉乃華, 謝耀德。2010。台灣人飲食與健康之趨勢:1993-1996 與 2005-2008 兩次營養健康調查之比較。
    連結:
  2. 潘思穎。2013。以脂肪細胞探討台灣藜中具調節血糖之活性成分。國立台灣大學生物資源暨農學院食品科技所碩士論文。
    連結:
  3. 黃伯超, 游素玲, 林月美, 朱志良。1992。我國成年人性別、年齡別、身高別 體重及過重與肥胖界定之探討。中華民國營養學會雜誌17:157-172
    連結:
  4. Ahima, R., & Flier, J. (2000). Adipose tissue as an endocrine organ. Trends Endocrinol MetabNLM , 11(8), 327-332.
    連結:
  5. Bhargava, A., Shukla, S., & Ohri, D. (2006). Chenopodium quinoa—An Indian perspective. IND CROP PROD, 23(1), 73-87.
    連結:
  6. Björntorp, P. (2009). Renaissance of a new frontier in OBES RES. Acta Med Scand, 196(1-6)
    連結:
  7. Boone, C., Mourot, J., Grégoire, F., & Remacle, C. (2000). The adipose conversion process: regulation by extracellular and intracellular factors. REPROD NUTR DEV, 40(4), 325-358.
    連結:
  8. Bost, F., Aouadi, M., Caron, L., & Binétruy, B. (2005). The role of MAPKs in adipocyte differentiation and obesity. BIOCHIMIE, 87(1), 51-56.
    連結:
  9. Brey, C., Nelder, M., Hailemariam, T., Gaugler, R., & Hashmi, S. (2009). Krüppel-like family of transcription factors: an emerging new frontier in fat biology. INT J BIOL SCI, 622-636.
    連結:
  10. Brown, A., Sun, L., Feramisco, J., Brown, M., & Goldstein, J. (2002). Cholesterol addition to ER membranes alters conformation of SCAP, the SREBP escort protein that regulates cholesterol metabolism. MOL CELL, 10(2), 237-245.
    連結:
  11. Cho, A., Jeon, S., Kim, M., Yeo, J., Seo, K., Choi, M., & Lee, M. (2010). Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice. FOOD CHEM TOXICOL, 48(3), 937-943.
    連結:
  12. Cypess, A., Lehman, S., Williams, G., Tal, I., Rodman, D., & Goldfine, A. et al. (2009). Identification and importance of brown adipose tissue in adult humans. OBSTET GYNECOL SURV, 64(8), 519-520.
    連結:
  13. Eaton, R., Berman, M., & Steinberg, D. (1969). Kinetic studies of plasma free fatty acid and triglyceride metabolism in man. J CLIN INVEST, 48(8), :1560-79.
    連結:
  14. Enerbäck, S. (2009). The origins of brown adipose tissue. NEW ENGL J MED, 360(19), 2021-2023.
    連結:
  15. Feng, B., Zhang, T., & Xu, H. (2013). Human adipose dynamics and metabolic health. ANN NY ACAD SCI, 1281(1), 160-177.
    連結:
  16. Floridon, C., Jensen, C., Thorsen, P., Nielsen, O., Sunde, L., & Westergaard, J. et al. (2000). Does Fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials? A study of FA1 in embryonic, fetal, and placental tissue and in maternal circulation. DIFFERENTIATION, 66(1), 49-59.
    連結:
  17. Ford, W., Honan, S., White, R., & Hiley, C. (2002). Evidence of a novel site mediating anandamide-induced negative inotropic and coronary vasodilatator responses in rat isolated hearts. BRIT J PHARMACOL, 135(5), 1191-1198.
    連結:
  18. Foucault, A., Mathé, V., Lafont, R., Even, P., Dioh, W., & Veillet, S. et al. (2012). Quinoa extract enriched in 20-hydroxyecdysone protects mice from diet-induced obesity and modulates adipokines expression. OBESITY (Silver Spring, Md), 20(2), 270-277.
    連結:
  19. Fredrikson, G., Tornqvist, H., & Belfrage, P. (1986). Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol. BIOCHIM BIOPHYS ACTA, 876(2), 288-293.
    連結:
  20. Freytag, S., Paielli, D., & Gilbert, J. (1994). Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells. GENE DEV, 8(14), 1654-1663.
    連結:
  21. Friedman, M. (1998). Fuel partitioning and food intake. AM J CLIN NUTR, (67), 513s-518s.
    連結:
  22. Frühbeck, G., Becerril, S., Sáinz, N., Garrastachu, P., & García-Velloso, M. (2009). BAT: a new target for human obesity?. Trends Pharmacol. Sci, 30(8), 387-396.
    連結:
  23. Glandt, M., & Raz, I. (2011). Present and future: pharmacologic treatment of obesity. INT J OBES, 2011(2011), 1-13.
    連結:
  24. Green, H., & Kehinde, O. (1974). Sublines of mouse 3T3 cells that accumulate lipid. CELL, 1(3), 113-116.
    連結:
  25. Green, H., & Kehinde, O. (1975). An established preadipose cell line and its differentiation in culture ii. factors affecting the adipose conversion. CELL, 5(1), 19-27.
    連結:
  26. Gregoire, F. (2001). Adipocyte differentiation: from fibroblast to endocrine cell. EXP BIOL MED, 226(11), 997-1002.
    連結:
  27. Grundy, S., Brewer, H., Cleeman, J., Smith, S., & Lenfant, C. (2004). Definition of metabolic syndrome: report of the national heart, lung, and blood institute/american heart association conference on scientific issues related to definition. ARTERIOSCLER THROMB VASC BIOL, 24(2), e13-e18.
    連結:
  28. Guerre-Millo, M. (2002). Adipose tissue hormones. J ENDOCRINOL INVEST, 25(10), 855-861.
    連結:
  29. Halder, S., Takemori, H., Hatano, O., Nonaka, Y., Wada, A., & Okamoto, M. (1998). Cloning of a membrane-spanning protein with epidermal growth factor-like repeat motifs from adrenal glomerulosa cells. ENDOCRINOLOGY, 139(7), 3316-3328.
    連結:
  30. Hawkins, R., & Clement, P. (1984). Development and construct validation of a self-report measure of binge eating tendencies. ADDICT BEHAV, 5(3), 219-226.
    連結:
  31. Hegele, R., Cao, H., Frankowski, C., Mathews, S., & Leff, T. (2002). PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. DIABETES, 51(12), 3586-3590.
    連結:
  32. Hirose, Y., Fujita, T., Ishii, T., & Ueno, N. (2010). Antioxidative properties and flavonoid composition of Chenopodium quinoa seeds cultivated in Japan. FOOD CHEM, 119(4), 1300-1306.
    連結:
  33. Hirsch, J., & Batchelor, B. (1976). Adipose tissue cellularity in human obesity. CLIN ENDOCRINOL MET, 5(2), 299-311.
    連結:
  34. Holm, C. (2003). Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. BIOCHEM SOC TRANS, 31(6), 1120-1124.
    連結:
  35. Horton, J., Goldstein, J., & Brown, M. (2002). SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J CLIN INVEST, 109(9), 1125-1131.
    連結:
  36. Hotamisligil, G., Arner, P., Caro, J., Atkinson, R., & Spiegelman, B. (1993). Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J CLIN INVEST, 95(5), 2409-2415.
    連結:
  37. Hsu, C., Huang, S., & Yen, G. (2006). Inhibitory effect of phenolic acids on the proliferation of 3T3-L1 preadipocytes in relation to their antioxidant activity. J AGRIC FOOD CHEM, 54(12), 4191-4197.
    連結:
  38. Ibrahim, M. (2010). Subcutaneous and visceral adipose tissue: structural and functional differences. OBES REV, 11(1), 11-18.
    連結:
  39. Isomaa, B., Almgren, P., Tuomi, T., Forsen, B., Lahti, K., Nissen, M. et al. (2001). Cardiovascular morbidity and mortality associated with the metabolic syndrome. DIABETES CARE, 24(4), 683-689.
    連結:
  40. James, P., Leach, R., Kalamara, E., & Shayeghi, M. (2001). The worldwide obesity epidemic. OBES RES, 9(S11), 228S-233S.
    連結:
  41. Kahn, B., & Flier, J. (2000). Obesity and insulin resistance. J CLIN INVEST, 106(4), 473-481.
    連結:
  42. Kern, P., Ranganathan, S., Li, C., Wood, L., & Ranganathan, G. (2001). Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. AM J PHYSIOL ENDOC M, 280(5), E745-751.
    連結:
  43. Kim, K., Kim, J., Wang, Y., & Sul, H. (2007). Pref-1 (Preadipocyte Factor 1) activates the MEK/Extracellular signal-regulated kinase pathway to inhibit adipocyte differentiation. MOL CELL BIOL, 27(6), 2294-2308.
    連結:
  44. Koutnikova, H., Cock, T., Watanabe, M., Houten, S., Champy, M., Dierich, A., & Auwerx, J. (2003). Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR hypomorphic mice. PROC NATL ACAD SCI U S A., 100(24), 14457-14462.
    連結:
  45. Lafontan, M., & Girard, J. (2008). Impact of visceral adipose tissue on liver metabolism. DIABETES OBES METAB, 34(4), 317-327.
    連結:
  46. Langin, D., Holm, C., & Lafontan, M. (1996). Adipocyte hormone-sensitive lipase: a major regulator of lipid metabolism. P NUTR SOC, 55(1B), 93-109.
    連結:
  47. Larder, R., Cheung, M., Tung, Y., Yeo, G., & Coll, A. (2011). Where to go with FTO?. TRENDS ENDOCRIN MET, 22(2), 53-59.
    連結:
  48. Lefterova, M., & Lazar, M. (2009). New developments in adipogenesis. TRENDS ENDOCRIN MET, 20(3), 107-114.
    連結:
  49. Linhart, H., Ishimura-Oka, K., DeMayo, F., Kibe, T., Repka, D., & Poindexter, B. et al. (2001). C/EBPalpha is required for differentiation of white, but not brown, adipose tissue. PROC NATL ACAD SCI U S A, (22), 12532-12537.
    連結:
  50. Manco, M., Calvani, M., & Mingrone, G. (2004). Effects of dietary fatty acids on insulin sensitivity and secretion. DIABETES OBES METAB, 6(6), 402-413.
    連結:
  51. Marrelli, M., Tudisco, R., Mastellone, V., & Conforti, F. (2013). A comparative study of phytochemical composition of genetically and non-genetically modified soybean (Glycine maxL.) and evaluation of antitumor activity. NAT PROD RES, 27(6),
    連結:
  52. Mayes, J., & Watson, G. (2004). Direct effects of sex steroid hormones on adipose tissues and obesity. OBES REV, 5(4), 197-216.
    連結:
  53. Mohamed-Ali, V., Goodrick, S., Rawesh, A., Katz, D., Miles, J., & Yudkin, J. et al. (1997). Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-α,in vivo. J CLIN ENDOCRINOL METAB, 82(12), 4196-4200.
    連結:
  54. Moller, D., & Flier, J. (1991). Insulin resistance--mechanisms, syndromes, and implications. N ENGL J MED, 325(13), 938-948.
    連結:
  55. Nielsen, S., Halliwill, J., Joyner, M., & Jensen, M. (2004). Vascular response to angiotensin ii in upper body obesity. HYPERTENSION, 44(4), 435-441.
    連結:
  56. Ntambi, J., & KIM, Y. (2000). Adipocyte differentiation and gene expression. J NUTR, (130), 3122-3126.
    連結:
  57. Pairault, J., & Green, H. (1979). A study of the adipose conversion of suspended 3T3 cells by using glycerophosphate dehydrogenase as differentiation marker. Proc Natl Acad Sci U S A., 76(10), 5138-5142.
    連結:
  58. Rangwala, S., & Lazar, M. (2000). Transcriptional control of adipogenesis. ANNU REV NUTR, 20(1), 535-559.
    連結:
  59. Richardson, J. (1952). The treatment of maternal obesity. LANCET, 259(6707), 525-528.
    連結:
  60. Robinson, J., & Newsholme, E. (1969). The effects of dietary conditions and glycerol concentration on glycerol uptake by rat liver and kidney-cortex slices. BIOCHEM J, 112(4), 449-453.
    連結:
  61. Rosen, E., Hsu, C., Wang, X., Sakai, S., Freeman, M., Gonzaiez, F., & Spiegeiman, B. (2002). C/EBPalpha induces adipogenesis through PPARgamma : a unified pathway. GENE DEV, 16(1), 22-26.
    連結:
  62. Ruales, J., & Nair, B. (1992). Nutritional quality of the protein in quinoa (Chenopodium quinoa, Willd) seeds. PLANT FOOD HUM NUTR, 42(1), 1-11.
    連結:
  63. Ruales, J., & Nair, B. (1993). Saponins, phytic acid, tannins and protease inhibitors in quinoa (Chenopodium quinoa, Willd) seeds. FOOD CHEM, 48(2), 137-143.
    連結:
  64. Ruiz-Hidalgo, M., Gubina, E., Tull, L., Baladrón, V., & Laborda, J. (2002). Dlk modulates mitogen-activated protein kinase signaling to allow or prevent differentiation. EXP CELL RES, 274(2), 178-188.
    連結:
  65. Scavo, L., Karas, M., Murray, M., & Leroith, D. (2004). Insulin-like growth factor-i stimulates both cell growth and lipogenesis during differentiation of human mesenchymal stem cells into adipocytes. J CLIN ENDOCRINOL METAB, 89(7), 3543-3553.
    連結:
  66. Sears, I., MacGinnitie, M., Kovacs, L., & Graves, R. (1996). Differentiation-dependent expression of the brown adipocyte uncoupling protein gene: regulation by peroxisome proliferator-activated receptor gamma. MOL CELL BIOL, 16(7), 3410-3419.
    連結:
  67. Smas, C., & Sul, H. (1993). Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation. CELL, 73(4), 725-734.
    連結:
  68. Taheri, S., Lin, L., Austin, D., Young, T., & Mignot, E. (2004). Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLOS MED, 1(3), e62.
    連結:
  69. Tontonoz, P., Hu, E., & Spiegelman, B. (1994). Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell, 79(7), 1147-1156.
    連結:
  70. Tsai, P., Chen, Y., Sheu, C., & Chen, C. (2011). Effect of nanogrinding on the pigment and bioactivity of Djulis (Chenopodium formosanum Koidz.). J AGRIC FOOD CHEM, 59(5), 1814-1820.
    連結:
  71. van Brummen, V., Vellenga, E., Swaanenburg, J., Fidler, V., Brummen, P., Kamps, W., & de Bont, E. (1999). Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia. BRIT J HAEMATOL, 107(2), 375-380.
    連結:
  72. van Marken Lichtenbelt, W., Vanhommerig, J., Smulders, N., Drossaerts, J., Kemerink, G., & Bouvy, N. et al. (2009). Cold-activated brown adipose tissue in healthy men. NEW ENGL J MED, 360(15), 1500-1508.
    連結:
  73. Virtanen, K., Lidell, M., Orava, J., Heglind, M., Westergren, R., & Niemi, T. et al. (2009). Functional Brown Adipose Tissue in Healthy Adults.NEW ENGL J MED, 360(11), 1518-1525.
    連結:
  74. Walther, T., & Farese, R. (2012). Lipid droplets and cellular lipid metabolism. ANNU REV BIOCHEM, 81(1), 687-714.
    連結:
  75. Wang, C., & Yang, G. (2010). Betacyanins from Portulaca oleracea L. ameliorate cognition deficits and attenuate oxidative damage induced by D-galactose in the brains of senescent mice. PHYTOMEDICINE, 17(7), 527-532.
    連結:
  76. Wang, N., Finegold, M., Bradley, A., Ou, C., Abdelsayed, S., & Wilde, M. et al. (1995). Impaired energy homeostasis in C/EBP alpha knockout mice. SCI, 269(5227), 1108-1112.
    連結:
  77. Wang, Y., & Sul, H. (2009). Pref-1 regulates mesenchymal cell commitment and differentiation through sox9. CELL METAB, 9(3), 287-302.
    連結:
  78. WILDING, J. (2006). Thiazolidinediones, insulin resistance and obesity: finding a balance. INT J CLIN PRACT, 60(10), 1272-1280.
    連結:
  79. Yao, Y., Zhu, Y., Gao, Y., Shi, Z., Hu, Y., & Ren, G. (2015). Suppressive effects of saponin-enriched extracts from quinoa on 3T3-L1 adipocyte differentiation. FOOD FUNCT., 6(10), 3282-3290.
    連結:
  80. Yeh, W., Bierer, B., & McKnight, S. (1995). Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells. Proc Natl Acad Sci U S A., 92(24), 11086-11090.
    連結:
  81. Zhang, H., Nøhr, J., Jensen, C., Petersen, R., Bachmann, E., & Teisner, B. et al. (2003). Insulin-like growth factor-1/insulin bypasses Pref-1/FA1-mediated inhibition of adipocyte differentiation. J BIOL CHEM, 278(23), 20906-20914
    連結:
  82. 台灣行政院衛生署。2006。肥胖與代謝症候群。基層醫學21 (12) 367-371。
  83. 林筱茜。2011。台灣藜萃取物抗致突變及抗氧化能力分析。嘉南藥理科技大學保健營養系碩士論文。
  84. 陳惠珍。2012。台灣藜不同植株部位與品種多酚化合物分布之探討。屏東科技大學食品科學系所碩士論文
  85. 梁智強。2006。分化流程對脂肪細胞特徵之影響。慈濟大學分子生物及細胞生物研究所碩士論文。
  86. 蔡碧仁, 郭耀綸, 楊遠波, 葛孟杰。2008。紅藜推廣手冊。
  87. 廖淑慧。2010。台灣藜不同顏色種子機能性成分之差異及降血脂功能性之評估。弘光科技大學食品暨應用生物科技所碩士論文。
  88. Karam, J., Sayegh, S., Nessim, F., Farag, A., & McFarlane, S. (2007). Medical management of obesity: an update. MINERVA ENDOCRINOL., 32(3), 185-207.
  89. Rosen, E., Walkey, C., Puigserver, P., & Spiegelman,, B. (2000). Transcriptional regulation of adipogenesis. GENE DEV, 14(11), 1293-1307.
  90. Solíz-Guerrero, J., Rodriguez, D., Rodríguez-García, R., Angulo-Sánchez, J., & Méndez-Padilla, G. (2002). Quinoa Saponins: concentration and composition analysis. TRENDS IN NEW CROPS AND NEW USES, (Eds J Janick, A Whipkey), pp.110-114 (ASHS Press: Alexandria, VA, USA).