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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77894完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
| dc.contributor.author | Yi-Ting Chuang | en |
| dc.contributor.author | 莊宜庭 | zh_TW |
| dc.date.accessioned | 2021-07-11T14:36:52Z | - |
| dc.date.available | 2022-09-04 | |
| dc.date.copyright | 2017-09-04 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-15 | |
| dc.identifier.citation | 1. Anders M. Näär, P.A.B., Sharleen Zhou,Shaji Abraham, William Solomon & Robert Tjian (1999). Composite co-activator ARC mediates chromatin-directed transcriptional activation.
2. Bewersdorf, J., Farese, R.V., Jr., and Walther, T.C. (2011). A new way to look at fat. Nat Methods 8, 132-133. 3. Bourbon, H.M., Aguilera, A., Ansari, A.Z., Asturias, F.J., Berk, A.J., Bjorklund, S., Blackwell, T.K., Borggrefe, T., Carey, M., Carlson, M., et al. (2004). A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II. Mol Cell 14, 553-557. 4. Brock, T.J., Browse, J., and Watts, J.L. (2006). Genetic regulation of unsaturated fatty acid composition in C. elegans. PLoS Genet 2, e108. 5. Brock, T.J., Browse, J., and Watts, J.L. (2007). Fatty acid desaturation and the regulation of adiposity in Caenorhabditis elegans. Genetics 176, 865-875. 6. Brown MS, G.J. (1997). The SREBP pathway regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. 7. Delrue M-A, M.J. (2004). Fat chance: genetic syndromes with obesity. 8. Elle, I.C., Olsen, L.C., Pultz, D., Rodkaer, S.V., and Faergeman, N.J. (2010). Something worth dyeing for: molecular tools for the dissection of lipid metabolism in Caenorhabditis elegans. FEBS Lett 584, 2183-2193. 9. Frayling, T.M., Timpson, N.J., Weedon, M.N., Zeggini, E., Freathy, R.M., Lindgren, C.M., Perry, J.R., Elliott, K.S., Lango, H., Rayner, N.W., et al. (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894. 10. Han, S., Schroeder, E.A., Silva-Garcia, C.G., Hebestreit, K., Mair, W.B., and Brunet, A. (2017). Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan. Nature 544, 185-190. 11. Hermine H. M. Maes, 2 Michael C. Neale,1 and Lindon J. Eaves (1997). Genetic and Environmental Factors in Relative Body Weight and Human Adiposity. 12. Hokari, R., Matsunaga, H., and Miura, S. (2013). Effect of dietary fat on intestinal inflammatory diseases. J Gastroenterol Hepatol 28 Suppl 4, 33-36. 13. Horton, J.D., Goldstein, J.L., and Brown, M.S. (2002). SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109, 1125-1131. 14. Iichiro Shimomura*, Y.B., Shinji Ikemoto, Jay D. Horton, Michael S. Brown†, and Joseph L. Goldstein† (1999). Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. 15. Jay D. Horton, N.A.S., Janet A. Warrington§, Norma N. Anderson*, Sahng Wook Park*, Michael S. Brown, and Joseph L. Goldstein (2003). Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. 16. Lee, D., Jeong, D.E., Son, H.G., Yamaoka, Y., Kim, H., Seo, K., Khan, A.A., Roh, T.Y., Moon, D.W., Lee, Y., et al. (2015). SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat. Genes Dev 29, 2490-2503. 17. Lee, J.N., and Ye, J. (2004). Proteolytic activation of sterol regulatory element-binding protein induced by cellular stress through depletion of Insig-1. J Biol Chem 279, 45257-45265. 18. Li, Y., Na, K., Lee, H.J., Lee, E.Y., and Paik, Y.K. (2011). Contribution of sams-1 and pmt-1 to lipid homoeostasis in adult Caenorhabditis elegans. J Biochem 149, 529-538. 19. Liang, B., Ferguson, K., Kadyk, L., and Watts, J.L. (2010). The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans. PLoS One 5, e9869. 20. MacNeil, L.T., Watson, E., Arda, H.E., Zhu, L.J., and Walhout, A.J. (2013). Diet-induced developmental acceleration independent of TOR and insulin in C. elegans. Cell 153, 240-252. 21. Mak, H.Y. (2012). Lipid droplets as fat storage organelles in Caenorhabditis elegans: Thematic Review Series: Lipid Droplet Synthesis and Metabolism: from Yeast to Man. J Lipid Res 53, 28-33. 22. Morihiro Matsuda, B.S.K., 1 Robert E. Hammer,2 Young-Ah Moon,1 Ryutaro Komuro,1, and Jay D. Horton, J.L.G., 1,3,4 Michael S. Brown,1,3,5 and Iichiro Shimomura1 (2001). SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. 23. Nomura, T., Horikawa, M., Shimamura, S., Hashimoto, T., and Sakamoto, K. (2010). Fat accumulation in Caenorhabditis elegans is mediated by SREBP homolog SBP-1. Genes Nutr 5, 17-27. 24. Novatchkova, M., and Eisenhaber, F. (2004). Linking transcriptional mediators via the GACKIX domain super family. Current Biology 14, R54-R55. 25. Ntambi, J. (2004). Regulation of stearoyl-CoA desaturases and role in metabolism. Progress in Lipid Research 43, 91-104. 26. Paradis, A.M., Godin, G., Perusse, L., and Vohl, M.C. (2009). Associations between dietary patterns and obesity phenotypes. Int J Obes (Lond) 33, 1419-1426. 27. Pathare, P.P., Lin, A., Bornfeldt, K.E., Taubert, S., and Van Gilst, M.R. (2012). Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships. PLoS Genet 8, e1002645. 28. Perez, C.L., and Van Gilst, M.R. (2008). A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans. Cell Metab 8, 266-274. 29. Pukkila-Worley, R., Feinbaum, R.L., McEwan, D.L., Conery, A.L., and Ausubel, F.M. (2014). The evolutionarily conserved mediator subunit MDT-15/MED15 links protective innate immune responses and xenobiotic detoxification. PLoS Pathog 10, e1004143. 30. Renée M. McKay, J.P.M., Leon Avery, and Jonathan M. Graff (2003). C. elegans: A Model for Exploring the Genetics of Fat Storage. 31. Shi, X., Li, J., Zou, X., Greggain, J., Rødkær, S.V., Færgeman, N.J., Liang, B., and Watts, J.L. (2013). Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase. Journal of Lipid Research 54, 2504-2514. 32. Srinivasan, S. (2015). Regulation of body fat in Caenorhabditis elegans. Annu Rev Physiol 77, 161-178. 33. Stefan Taubert, M.R.V.G., 1,3 Malene Hansen,2 and Keith R. Yamamoto (2006). A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans. . Genome Res 12, 47-56. 34. Svensk, E., Stahlman, M., Andersson, C.H., Johansson, M., Boren, J., and Pilon, M. (2013). PAQR-2 regulates fatty acid desaturation during cold adaptation in C. elegans. PLoS Genet 9, e1003801. 35. Taubert, S., Hansen, M., Van Gilst, M.R., Cooper, S.B., and Yamamoto, K.R. (2008). The Mediator subunit MDT-15 confers metabolic adaptation to ingested material. PLoS Genet 4, e1000021. 36. Venters, B.J., and Pugh, B.F. (2009). How eukaryotic genes are transcribed. Crit Rev Biochem Mol Biol 44, 117-141. 37. Vrablik, T.L., Petyuk, V.A., Larson, E.M., Smith, R.D., and Watts, J.L. (2015). Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein. Biochim Biophys Acta 1851, 1337-1345. 38. Walker, A.K., Jacobs, R.L., Watts, J.L., Rottiers, V., Jiang, K., Finnegan, D.M., Shioda, T., Hansen, M., Yang, F., Niebergall, L.J., et al. (2011). A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans. Cell 147, 840-852. 39. Walker, A.K., Yang, F., Jiang, K., Ji, J.Y., Watts, J.L., Purushotham, A., Boss, O., Hirsch, M.L., Ribich, S., Smith, J.J., et al. (2010). Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev 24, 1403-1417. 40. Watts, J.L. (2009). Fat synthesis and adiposity regulation in Caenorhabditis elegans. Trends Endocrinol Metab 20, 58-65. 41. Watts JL, B.J. (2002). Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans. 42. Watts, J.L., and Browse, J. (2000). A palmitoyl-CoA-specific delta9 fatty acid desaturase from Caenorhabditis elegans. Biochem Biophys Res Commun 272, 263-269. 43. Wong, J., Quinn, C.M., and Brown, A.J. (2006). SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR. Biochem J 400, 485-491. 44. Yang, F., Vought, B.W., Satterlee, J.S., Walker, A.K., Jim Sun, Z.Y., Watts, J.L., DeBeaumont, R., Saito, R.M., Hyberts, S.G., Yang, S., et al. (2006). An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature 442, 700-704. 45. Castro, C., Sar, F., Shaw, W.R., Mishima, M., Miska, E.A., and Griffin, J.L. (2012). A metabolomic strategy defines the regulation of lipid content and global metabolism by Delta9 desaturases in Caenorhabditis elegans. BMC Genomics 13, 36. 46. Kadandale, P., Chatterjee, I., and Singson, A. (2009). Germline transformation of Caenorhabditis elegans by injection. Methods Mol Biol 518, 123-133. 47. Savory, F.R., Sait, S.M., and Hope, I.A. (2011). DAF-16 and Delta9 desaturase genes promote cold tolerance in long-lived Caenorhabditis elegans age-1 mutants. PLoS One 6, e24550. 48. Bewersdorf, J., Farese, R.V., Jr., and Walther, T.C. (2011). A new way to look at fat. Nat Methods 8, 132-133. 49. Brock, T.J., Browse, J., and Watts, J.L. (2006). Genetic regulation of unsaturated fatty acid composition in C. elegans. PLoS Genet 2, e108. 50. Castro, C., Sar, F., Shaw, W.R., Mishima, M., Miska, E.A., and Griffin, J.L. (2012). A metabolomic strategy defines the regulation of lipid content and global metabolism by Delta9 desaturases in Caenorhabditis elegans. BMC Genomics 13, 36. 51. Kaveh Ashrafi, F.Y.C., Jennifer L. Watts, Andrew G. Fraser, Ravi S. Kamath, Julie Ahringer & Gary Ruvkun (2002). Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. 52. Lee, D., Jeong, D.E., Son, H.G., Yamaoka, Y., Kim, H., Seo, K., Khan, A.A., Roh, T.Y., Moon, D.W., Lee, Y., et al. (2015). SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat. Genes Dev 29, 2490-2503. 53. MacNeil, L.T., Watson, E., Arda, H.E., Zhu, L.J., and Walhout, A.J. (2013). Diet-induced developmental acceleration independent of TOR and insulin in C. elegans. Cell 153, 240-252. 54. Murray P1, H.S., Govan GG, Gracey AY, Cossins AR. (2007). An explicit test of the phospholipid saturation hypothesis of acquired cold tolerance in Caenorhabditis elegans. 55. Nomura, T., Horikawa, M., Shimamura, S., Hashimoto, T., and Sakamoto, K. (2010). Fat accumulation in Caenorhabditis elegans is mediated by SREBP homolog SBP-1. Genes Nutr 5, 17-27. 56. Ntambi, J. (2004). Regulation of stearoyl-CoA desaturases and role in metabolism. Progress in Lipid Research 43, 91-104. 57. Paton, C.M., and Ntambi, J.M. (2009). Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab 297, E28-37. 58. Peng Zhang, H.N., Zhenglong Liu, Shuyan Zhang, Peng Xue,, Yong Chen, J.P., Gong Peng, Xun Huang, Fuquan Yang, Zhensheng Xie,, and Tao Xu, P.X., Guangshuo Ou, Shaobing O. Zhang, and Pingsheng Liu (2012). Proteomic Study and Marker Protein Identification of Caenorhabditis elegans Lipid Droplets. 59. Pilon, M., and Svensk, E. (2013). PAQR-2 may be a regulator of membrane fluidity during cold adaptation. Worm 2, e27123. 60. Savory, F.R., Sait, S.M., and Hope, I.A. (2011). DAF-16 and Delta9 desaturase genes promote cold tolerance in long-lived Caenorhabditis elegans age-1 mutants. PLoS One 6, e24550. 61. Taubert, S., Hansen, M., Van Gilst, M.R., Cooper, S.B., and Yamamoto, K.R. (2008). The Mediator subunit MDT-15 confers metabolic adaptation to ingested material. PLoS Genet 4, e1000021. 62. Testerink, N., van der Sanden, M.H., Houweling, M., Helms, J.B., and Vaandrager, A.B. (2009). Depletion of phosphatidylcholine affects endoplasmic reticulum morphology and protein traffic at the Golgi complex. J Lipid Res 50, 2182-2192. 63. Walker, A.K., Jacobs, R.L., Watts, J.L., Rottiers, V., Jiang, K., Finnegan, D.M., Shioda, T., Hansen, M., Yang, F., Niebergall, L.J., et al. (2011). A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans. Cell 147, 840-852. 64. Watts, J.L., and Browse, J. (2000). A palmitoyl-CoA-specific delta9 fatty acid desaturase from Caenorhabditis elegans. Biochem Biophys Res Commun 272, 263-269. 65. Anders M. Näär, P.A.B., Sharleen Zhou,Shaji Abraham, William Solomon & Robert Tjian (1999). Composite co-activator ARC mediates chromatin-directed transcriptional activation. 66. Bewersdorf, J., Farese, R.V., Jr., and Walther, T.C. (2011). A new way to look at fat. Nat Methods 8, 132-133. 67. Bourbon, H.M., Aguilera, A., Ansari, A.Z., Asturias, F.J., Berk, A.J., Bjorklund, S., Blackwell, T.K., Borggrefe, T., Carey, M., Carlson, M., et al. (2004). A unified nomenclature for protein subunits of mediator complexes linking transcriptional regulators to RNA polymerase II. Mol Cell 14, 553-557. 68. Brock, T.J., Browse, J., and Watts, J.L. (2006). Genetic regulation of unsaturated fatty acid composition in C. elegans. PLoS Genet 2, e108. 69. Brock, T.J., Browse, J., and Watts, J.L. (2007). Fatty acid desaturation and the regulation of adiposity in Caenorhabditis elegans. Genetics 176, 865-875. 70. Brown MS, G.J. (1997). The SREBP pathway regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. 71. Browse, J.L.W.a.J. (2002). Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans. 72. Castro, C., Sar, F., Shaw, W.R., Mishima, M., Miska, E.A., and Griffin, J.L. (2012). A metabolomic strategy defines the regulation of lipid content and global metabolism by Delta9 desaturases in Caenorhabditis elegans. BMC Genomics 13, 36. 73. Delrue M-A, M.J. (2004). Fat chance: genetic syndromes with obesity. 74. Elle, I.C., Olsen, L.C., Pultz, D., Rodkaer, S.V., and Faergeman, N.J. (2010). Something worth dyeing for: molecular tools for the dissection of lipid metabolism in Caenorhabditis elegans. FEBS Lett 584, 2183-2193. 75. Frayling, T.M., Timpson, N.J., Weedon, M.N., Zeggini, E., Freathy, R.M., Lindgren, C.M., Perry, J.R., Elliott, K.S., Lango, H., Rayner, N.W., et al. (2007). A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889-894. 76. Han, S., Schroeder, E.A., Silva-Garcia, C.G., Hebestreit, K., Mair, W.B., and Brunet, A. (2017). Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan. Nature 544, 185-190. 77. Hermine H. M. Maes, 2 Michael C. Neale,1 and Lindon J. Eaves (1997). Genetic and Environmental Factors in Relative Body Weight and Human Adiposity. 78. Hokari, R., Matsunaga, H., and Miura, S. (2013). Effect of dietary fat on intestinal inflammatory diseases. J Gastroenterol Hepatol 28 Suppl 4, 33-36. 79. Horton, J.D., Goldstein, J.L., and Brown, M.S. (2002). SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109, 1125-1131. 80. Hou, N.S., Gutschmidt, A., Choi, D.Y., Pather, K., Shi, X., Watts, J.L., Hoppe, T., and Taubert, S. (2014). Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo. Proc Natl Acad Sci U S A 111, E2271-2280. 81. Iichiro Shimomura, Y.B., Shinji Ikemoto, Jay D. Horton, Michael S. Brown†, and Joseph L. Goldstein (1999). Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. 82. Jay D. Horton, N.A.S., Janet A. Warrington§, Norma N. Anderson*, Sahng Wook Park*, Michael S. Brown, and Joseph L. Goldstein (2003). Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. 83. Kadandale, P., Chatterjee, I., and Singson, A. (2009). Germline transformation of Caenorhabditis elegans by injection. Methods Mol Biol 518, 123-133. 84. Kaveh Ashrafi, F.Y.C., Jennifer L. Watts, Andrew G. Fraser, Ravi S. Kamath, Julie Ahringer & Gary Ruvkun (2002). Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. 85. Lee, D., Jeong, D.E., Son, H.G., Yamaoka, Y., Kim, H., Seo, K., Khan, A.A., Roh, T.Y., Moon, D.W., Lee, Y., et al. (2015). SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat. Genes Dev 29, 2490-2503. 86. Lee, J.N., and Ye, J. (2004). Proteolytic activation of sterol regulatory element-binding protein induced by cellular stress through depletion of Insig-1. J Biol Chem 279, 45257-45265. 87. Li, Y., Na, K., Lee, H.J., Lee, E.Y., and Paik, Y.K. (2011). Contribution of sams-1 and pmt-1 to lipid homoeostasis in adult Caenorhabditis elegans. J Biochem 149, 529-538. 88. Liang, B., Ferguson, K., Kadyk, L., and Watts, J.L. (2010). The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans. PLoS One 5, e9869. 89. MacNeil, L.T., Watson, E., Arda, H.E., Zhu, L.J., and Walhout, A.J. (2013). Diet-induced developmental acceleration independent of TOR and insulin in C. elegans. Cell 153, 240-252. 90. Madeleine Ehmke, K.L., Ralf Schnabel, and Frank Döring (2014). S-Adenosyl methionine synthetase 1 limits fat storage in Caenorhabditis elegans. 91. Mak, H.Y. (2012). Lipid droplets as fat storage organelles in Caenorhabditis elegans: Thematic Review Series: Lipid Droplet Synthesis and Metabolism: from Yeast to Man. J Lipid Res 53, 28-33. 92. Miller, C., Matic, I., Maier, K.C., Schwalb, B., Roether, S., Strasser, K., Tresch, A., Mann, M., and Cramer, P. (2012). Mediator phosphorylation prevents stress response transcription during non-stress conditions. J Biol Chem 287, 44017-44026. 93. Morihiro Matsuda, B.S.K., 1 Robert E. Hammer,2 Young-Ah Moon,1 Ryutaro Komuro,1, and Jay D. Horton, J.L.G., 1,3,4 Michael S. Brown,1,3,5 and Iichiro Shimomura1 (2001). SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. 94. Murray P1, H.S., Govan GG, Gracey AY, Cossins AR. (2007). An explicit test of the phospholipid saturation hypothesis of acquired cold tolerance in Caenorhabditis elegans. 95. Nomura, T., Horikawa, M., Shimamura, S., Hashimoto, T., and Sakamoto, K. (2010). Fat accumulation in Caenorhabditis elegans is mediated by SREBP homolog SBP-1. Genes Nutr 5, 17-27. 96. Novatchkova, M., and Eisenhaber, F. (2004). Linking transcriptional mediators via the GACKIX domain super family. Current Biology 14, R54-R55. 97. Ntambi, J. (2004). Regulation of stearoyl-CoA desaturases and role in metabolism. Progress in Lipid Research 43, 91-104. 98. Paradis, A.M., Godin, G., Perusse, L., and Vohl, M.C. (2009). Associations between dietary patterns and obesity phenotypes. Int J Obes (Lond) 33, 1419-1426. 99. Pathare, P.P., Lin, A., Bornfeldt, K.E., Taubert, S., and Van Gilst, M.R. (2012). Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships. PLoS Genet 8, e1002645. 100. Paton, C.M., and Ntambi, J.M. (2009). Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab 297, E28-37. 101. Peng Zhang, H.N., Zhenglong Liu, Shuyan Zhang, Peng Xue,, Yong Chen, J.P., Gong Peng, Xun Huang, Fuquan Yang, Zhensheng Xie,, and Tao Xu, P.X., Guangshuo Ou, Shaobing O. Zhang, and Pingsheng Liu (2012). Proteomic Study and Marker Protein Identification of Caenorhabditis elegans Lipid Droplets. 102. Perez, C.L., and Van Gilst, M.R. (2008). A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans. Cell Metab 8, 266-274. 103. Pilon, M., and Svensk, E. (2013). PAQR-2 may be a regulator of membrane fluidity during cold adaptation. Worm 2, e27123. 104. Pukkila-Worley, R., Feinbaum, R.L., McEwan, D.L., Conery, A.L., and Ausubel, F.M. (2014). The evolutionarily conserved mediator subunit MDT-15/MED15 links protective innate immune responses and xenobiotic detoxification. PLoS Pathog 10, e1004143. 105. Renée M. McKay, J.P.M., Leon Avery, and Jonathan M. Graff (2003). C. elegans: A Model for Exploring the Genetics of Fat Storage. 106. Savory, F.R., Sait, S.M., and Hope, I.A. (2011). DAF-16 and Delta9 desaturase genes promote cold tolerance in long-lived Caenorhabditis elegans age-1 mutants. PLoS One 6, e24550. 107. Shi, X., Li, J., Zou, X., Greggain, J., Rødkær, S.V., Færgeman, N.J., Liang, B., and Watts, J.L. (2013). Regulation of lipid droplet size and phospholipid composition by stearoyl-CoA desaturase. Journal of Lipid Research 54, 2504-2514. 108. Srinivasan, S. (2015). Regulation of body fat in Caenorhabditis elegans. Annu Rev Physiol 77, 161-178. 109. Stefan Taubert, M.R.V.G., 1,3 Malene Hansen,2 and Keith R. Yamamoto (2006). A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans. . Genome Res 12, 47-56. 110. Svensk, E., Stahlman, M., Andersson, C.H., Johansson, M., Boren, J., and Pilon, M. (2013). PAQR-2 regulates fatty acid desaturation during cold adaptation in C. elegans. PLoS Genet 9, e1003801. 111. Taubert, S., Hansen, M., Van Gilst, M.R., Cooper, S.B., and Yamamoto, K.R. (2008). The Mediator subunit MDT-15 confers metabolic adaptation to ingested material. PLoS Genet 4, e1000021. 112. Testerink, N., van der Sanden, M.H., Houweling, M., Helms, J.B., and Vaandrager, A.B. (2009). Depletion of phosphatidylcholine affects endoplasmic reticulum morphology and protein traffic at the Golgi complex. J Lipid Res 50, 2182-2192. 113. Van Gilst, M.R., Hadjivassiliou, H., Jolly, A., and Yamamoto, K.R. (2005). Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans. PLoS Biol 3, e53. 114. Venters, B.J., and Pugh, B.F. (2009). How eukaryotic genes are transcribed. Crit Rev Biochem Mol Biol 44, 117-141. 115. Vrablik, T.L., Petyuk, V.A., Larson, E.M., Smith, R.D., and Watts, J.L. (2015). Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein. Biochim Biophys Acta 1851, 1337-1345. 116. Walker, A.K., Jacobs, R.L., Watts, J.L., Rottiers, V., Jiang, K., Finnegan, D.M., Shioda, T., Hansen, M., Yang, F., Niebergall, L.J., et al. (2011). A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans. Cell 147, 840-852. 117. Walker, A.K., Yang, F., Jiang, K., Ji, J.Y., Watts, J.L., Purushotham, A., Boss, O., Hirsch, M.L., Ribich, S., Smith, J.J., et al. (2010). Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev 24, 1403-1417. 118. Watts, J.L. (2009). Fat synthesis and adiposity regulation in Caenorhabditis elegans. Trends Endocrinol Metab 20, 58-65. 119. Watts JL, B.J. (2002). Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans. 120. Watts, J.L., and Browse, J. (2000). A palmitoyl-CoA-specific delta9 fatty acid desaturase from Caenorhabditis elegans. Biochem Biophys Res Commun 272, 263-269. 121. Wong, J., Quinn, C.M., and Brown, A.J. (2006). SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR. Biochem J 400, 485-491. 122. Yang, F., Vought, B.W., Satterlee, J.S., Walker, A.K., Jim Sun, Z.Y., Watts, J.L., DeBeaumont, R., Saito, R.M., Hyberts, S.G., Yang, S., et al. (2006). An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature 442, 700-704. 123. Yang, F., Vought, B.W., Satterlee, J.S., Walker, A.K., Jim Sun, Z.Y., Watts, J.L., DeBeaumont, R., Saito, R.M., Hyberts, S.G., Yang, S., et al. (2006). An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature 442, 700-704. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77894 | - |
| dc.description.abstract | 隨著健康知識的普及，國人逐漸重視飲食裡的成分標示，食物所提供之營養素對於維持生物體內的恆定至關重要。在許多模式生物中都已證實飲食會影響到生物之生育、發育、老化等生理行為，然而其中詳細的分子機制還尚未明朗。利用ORO染色技術發現餵食Comamonas DA1877的線蟲(C. elegans) 其體內的脂肪含量比餵食標準食物E. coli OP50的線蟲還要少。因此我們利用餵食這兩種不同食物的線蟲探討飲食如何影響生物體內的脂肪代謝。我的研究中發現，線蟲體內磷脂醯膽鹼(phosphatidylcholine)的含量上升是導致DA1877餵食之三酸甘油脂(triacylglycerol)含量下降的原因之一，我們進一步發現DA1877飲食造成磷脂醯膽鹼所調控的固醇調節區域結合蛋白(SBP-1) 的脂肪生成功能的缺失。在DA1877餵食下SBP-1並沒有改變其在細胞核的表現量，因此我們認為 SBP-1進入細胞核內所需的活化過程和DA1877餵食下線蟲脂肪含量減少無關。有趣的是我們發現了SBP-1核內的轉錄輔激活因子MDT-15參與在飲食調控之脂肪含量改變。雖然mdt-15突變和sbp-1突變的線蟲在不同細菌餵食下對脂肪含量有不一樣的效果，但這可能是由於mdt-15在不同飲食下經由與不同脂肪代謝轉錄因子結合所致。我們經由檢視mdt-15的目標基因：脂肪酸去飽和酶(fatty acid desaturase): fat-5, fat-6 和fat-7發現DA1877的餵食導致fat-5 與 fat-7表現下降，但不影響fat-6。我們更進一步利用mdt-15突變證明在不同的細菌餵食下mdt-15對此兩基因展現不同的調控。此外，我們也發現相較於餵食OP50，DA1877能夠使mdt-15突變之線蟲保有更多的子代，這個現象也暗示著不同細菌餵食下的線蟲對mdt-15有著不同的需求。另外，我們發現mdt-15突變的線蟲其S-腺苷甲硫氨酸合成酶(sams-1)表現量被抑制了，而mdt-15是否透過調控sams-1來影響脂肪利用還待進一步的實驗釐清。另一方面，在冷昏迷(cold coma)實驗中發現，吃DA1877的線蟲適應寒冷環境的能力明顯下降，然而僅僅限制fat-5和fat-7表現量並不足以影響線蟲適應低溫的能力，氣相層析質譜(GC/MS)的結果顯示出DA1877餵食之線蟲體內有較少的多元不飽和脂肪酸(poly-unsaturated fatty acids)，這可能便是DA1877餵食之線蟲無法適應低溫的原因。我的研究結果顯示: 飲食會影響生物體的脂肪新陳代謝系統包含各種脂肪的組成比例，進而改變生物體的脂質恆定(lipid homeostasis)。 而mdt-15在不同飲食造成的脂肪代謝差異扮演了相當重要的角色，然而飲食如何調控mdt-15還需要我們更深入的探討。 | zh_TW |
| dc.description.abstract | Dietary effects on lifespan, development, fertility and other physiological processes have been shown in many model animals. Nevertheless, the underlying mechanisms remained largely unknown. In our lab, we fed Caenorhabditis elegans with an alternative bacteria Comamonas DA1877 and found that animals exhibited reduced fat storage by Oil Red O (ORO) stain compared to ones fed with the standard bacteria E. coli OP50. We performed thin-layer chromatography (TLC) analysis and found the lower level of triacylglycerol (TAG), the major lipid form for fat storage, and the increased level in phosphatidylcholine (PC), the dominant component of membrane phospholipids in DA1877-fed animals, indicating a dramatic lipid metabolism change mediated by diets. By abolishing PC synthesis, we demonstrated the increased PC level is the cause for DA1877-mediated lipid reduction. To understand how PC level regulates lipid content in DA1877-fed animals, we tested the regulation of lipogenic transcription factor SBP-1 on different diets. Loss of sbp-1 reduced the fat level in OP50-fed animals but not DA1877-fed ones. In addition, overexpressed SBP-1 restored lipid content reduction mediated by DA1877 diet. We further demonstrated the similar intensity of the intestinal nuclear GFP::SBP-1 in both DA1877- and OP50- fed animals, suggesting the constrained sbp-1-dependent lipogenesis on DA1877 is not through inhibiting sbp-1 nuclear localization. Intriguingly, loss of mdt-15, the sbp-1 co-activator, not only increased fat content but also enlarged the lipid droplet size compared to wild-type fed DA1877, while mdt-15 reduced lipid content in OP50-fed animals. Moreover, DA1877 diet resulted in decreased expression of fat-5 and fat-7 but not fat-6, all of which are mdt-15 target genes. By mdt-15 deficiency, we demonstrated that mdt-15 regulated its target genes, differentially on different diets, possibly via interaction with different transcription factors in regulation of lipid metabolism. In addition, we found mdt-15 might regulate lipid content through modulating the expression of sams-1, an important gene in methylation cycle. Last but not least, DA1877-fed worms exhibited poor ability to resist cold stress, suggesting the alteration of membrane fluidity. Gas chromatography–mass spectrometry (GC-MS) analysis revealed different diets changed worm lipid composition as DA1877-fed worms showed poor contents of polyunsaturated fatty acids (PUFAs) and more saturated fatty acids (SFAs) than OP50-fed worms. Together, our results proposed that diets affect lipid composition to regulate lipid level in C. elegans. The fat content reduction is caused by the relative high PC level in DA1877-fed animals and mdt-15 is identified to play a key role in the dietary-dependent lipid regulation mechanism. By dissecting different mdt-15 binding partners on different diets, it is anticipated to delineate how different diet affect lipid homeostasis in C. elegans. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:36:52Z (GMT). No. of bitstreams: 1 ntu-106-R04b43011-1.pdf: 2866945 bytes, checksum: 0d4067568f0ccebdee8c971e634f525c (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 口試委員會審定書
誌謝……………………………………………………………………….……………I 中文摘要……………………………………………………………….……………II Abstract…………………………………………………………………...…………IV Introduction……………………………………………………………….….………1 Diets affect fat metabolism in the organisms……………………………..………1 Dietary effects on worms…………………………………………..…..…………2 SREBPs/SBP-1……………………………………………………….….………4 MED-15/MDT-15………………………………………………………….….…6 Material and Methods………………………………………………………………12 C. elegans strains…………………………………………………………..……12 Construction of mdt-15 translational GFP fusions and microinjection……….…13 Bacterial strains and plates preparation………………………………...….……14 C. elegans synchronization……………………………………………..….……15 GFP reporter analysis and quantification…………………………………..……15 Immunostaining…………………………………………………..……….……16 Oil Red O staining and quantification…………………………………….…..…18 Lipid extraction…………………………………………………………………19 Thin Layer Chromatography analysis…………………………………….…..…20 Gas Chromatography Analysis for Fatty Acid Profiling………………….…..…21 Cold coma recovery assay………………………………………………………22 Bodipy 493/503 staining for imaging………………………………..……….…22 Results…………………………………………………………………………….…24 1. DA1877-fed worms showed less triacylglycerol and more phosphatidylcholine………………………………………………….……24 2. Reduction of phosphatidylcholine level suppressed DA1877-mediated fat content reduction…………………………………………………………..25 3. DA1877-mediated fat reduction could be caused by inhibition of SBP-1...27 4. SBP-1 appeared accumulation in intestinal nuclei at a similar level in OP50 and DA1877-fed animals…………………………………………….……29 5. mdt-15 participates in the fat content reduction in DA1877-fed worms……………………………………………………………………...30 6. Δ9-desaturase genes fat-5 and fat-7 showed lower expression in DA1877-fed animals…………………………………………………………...……32 7. mdt-15 regulates sams-1, encoding S-adenosylmethionine synthase 1, on both diets……………………………………………………………..……33 8. DA1877-fed worms showed slower recovery from cold shock……...……33 9. DA1877-fed animals showed less PUFAs and more SFAs compared to OP50-fed ones………………………………………………………..……35 Discussion……………………………………………………………………………36 The relationship between mdt-15 and phosphatidylcholine in DA1877-fed worms ………………………………………. ………………………….……36 DA1877 rescues the embryonic lethality of mdt-15, acdh-1 and nhr-68…….…38 mdt-15 may regulated different target genes on different diets……………...…39 Figures…………………………………………………………………………….…40 Figure 1. DA1877-fed animals have a lower TAG level and a higher PC level compared to OP50-fed ones…………………………………………….………40 Figure 2. cept-1(et10) showed no effects on relative fat content and PC level compare to wild-type…………………………………………………...………41 Figure 3. pcyt-1(et9) showed increased fat content on DA1877 diet……...……42 Figure 4. sbp-1-dependent lipogenesis is dietary-specific, and overexpression of sbp-1 rescues the low fat content on DA1877 diet……………………..………43 Figure 5. GFP::SBP-1 are present in intestinal nuclei at a similar level on both diets…………………………………………………………………………..…45 Figure 6. mdt-15 reduces the fat content relative to wild-type on OP50 diet, but increases the fat content compared to wild-type on DA1877 diet………..…...…47 Figure 7. DA1877 diet causes reduced fat-5 and fat-7 expression levels compared to OP50…………….……………………………………………………………54 Figure 8. mdt-15(tm2182) showed reduced expression of both fat-5 and fat-7 on OP50 diet, but only reduced fat-7, not fat-5 on DA1877 diet………………..…55 Figure 9. DA1877 rescued the fertility defect in mdt-15(tm2182) mutant worms…………………………………………………………………………...57 Figure 10. mdt-15(tm2182) reduces the expression of sams-1 on both diets...…58 Figure 11. DA1877 diet relative to OP50 diet resulted in longer recovery time in the worms………………………………………………………………….……59 Figure 12. Relative fatty acid composition of DA1877 fed worms compared to ones grown on OP50 diet…….………………………………………………….60 Supplementary…………………………….…………………………………...……61 Figure S1. fat-5 and fat-7 double mutations increased fat content significantly in DA1877 -fed animals……………………………………………………..……61 Figure S2. sams-1 and pcyt-1 exhibited large vacuoles in intestine on DA1877 diet.………………………..……………..………………………………..……64 Figure S3. Proposed model in fat regulation on DA1877 diet…….……….……66 Reference…………………………………………………………………….………67 | |
| dc.language.iso | en | |
| dc.subject | 脂肪含量 | zh_TW |
| dc.subject | mdt-15 | zh_TW |
| dc.subject | sbp-1 | zh_TW |
| dc.subject | 脂肪新陳代謝 | zh_TW |
| dc.subject | 脂肪酸組成 | zh_TW |
| dc.subject | sbp-1 | en |
| dc.subject | mdt-15 | en |
| dc.subject | fat content | en |
| dc.subject | fatty acid composition | en |
| dc.subject | lipid metabolism | en |
| dc.title | 飲食調節之線蟲脂肪新陳代謝 | zh_TW |
| dc.title | Dietary effects on lipid metabolism in C. elegans | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王昭雯(Chao-Wen Wang),蔡欣祐(Hsin-Yue Tsai),許翱麟(Ao-Lin Hsu),金翠庭(Tsiu-Ting Ching) | |
| dc.subject.keyword | mdt-15,sbp-1,脂肪新陳代謝,脂肪酸組成,脂肪含量, | zh_TW |
| dc.subject.keyword | mdt-15,sbp-1,lipid metabolism,fatty acid composition,fat content, | en |
| dc.relation.page | 76 | |
| dc.identifier.doi | 10.6342/NTU201703096 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-15 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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