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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 王培育 | |
dc.contributor.author | Wei-Sheng Lin | en |
dc.contributor.author | 林為聖 | zh_TW |
dc.date.accessioned | 2021-06-08T02:04:16Z | - |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-02-22 | |
dc.identifier.citation | Apidianakis, Y., & Rahme, L. G. (2011). Drosophila melanogaster as a model for human intestinal infection and pathology. Dis Model Mech, 4(1), 21-30.
Banerjee, K. K., Ayyub, C., Sengupta, S., & Kolthur-Seetharam, U. (2012). dSir2 deficiency in the fatbody, but not muscles, affects systemic insulin signaling, fat mobilization and starvation survival in flies. Aging (Albany NY), 4(3), 206-223. Barlow, G. M., Yu, A., & Mathur, R. (2015). Role of the Gut Microbiome in Obesity and Diabetes Mellitus. Nutr Clin Pract, 30(6), 787-797. Bharucha, K. N. (2009). The epicurean fly: using Drosophila melanogaster to study metabolism. Pediatr Res, 65(2), 132-137. Birse, R. T., Choi, J., Reardon, K., Rodriguez, J., Graham, S., Diop, S., . . . Oldham, S. (2010). High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. Cell Metab, 12(5), 533-544. Bohm, M., Siwiec, R. M., & Wo, J. M. (2013). Diagnosis and management of small intestinal bacterial overgrowth. Nutr Clin Pract, 28(3), 289-299. Brand, A. H., & Perrimon, N. (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development, 118(2), 401-415. Buchon, N., Broderick, N. A., & Lemaitre, B. (2013a). Gut homeostasis in a microbial world: insights from Drosophila melanogaster. Nat Rev Microbiol, 11(9), 615-626. Buchon, N., Osman, D., David, F. P., Fang, H. Y., Boquete, J. P., Deplancke, B., & Lemaitre, B. (2013b). Morphological and molecular characterization of adult midgut compartmentalization in Drosophila. Cell Rep, 3(5), 1725-1738. Canani, R. B., & Terrin, G. (2010). Gastric acidity inhibitors and the risk of intestinal infections. Curr Opin Gastroenterol, 26(1), 31-35. Clancy, D. J., Gems, D., Harshman, L. G., Oldham, S., Stocker, H., Hafen, E., . . . Partridge, L. (2001). Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science, 292(5514), 104-106. Compare, D., Pica, L., Rocco, A., De Giorgi, F., Cuomo, R., Sarnelli, G., . . . Nardone, G. (2011). Effects of long-term PPI treatment on producing bowel symptoms and SIBO. Eur J Clin Invest, 41(4), 380-386. Djawdan, M., Chippindale, A. K., Rose, M. R., & Bradley, T. J. (1998). Metabolic reserves and evolved stress resistance in Drosophila melanogaster. Physiol Zool, 71(5), 584-594. Doroszuk, A., Jonker, M. J., Pul, N., Breit, T. M., & Zwaan, B. J. (2012). Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension. BMC Genomics, 13, 167. Dubreuil, R. R. (2004). Copper cells and stomach acid secretion in the Drosophila midgut. The International Journal of Biochemistry & Cell Biology, 36(5), 742-752. Dubreuil, R. R., Frankel, J., Wang, P., Howrylak, J., Kappil, M., & Grushko, T. A. (1998). Mutations of alpha spectrin and labial block cuprophilic cell differentiation and acid secretion in the middle midgut of Drosophila larvae. Dev Biol, 194(1), 1-11. Erkosar, B., Defaye, A., Bozonnet, N., Puthier, D., Royet, J., & Leulier, F. (2014). Drosophila microbiota modulates host metabolic gene expression via IMD/NF-kappaB signaling. PLoS One, 9(4), e94729. Erkosar, B., & Leulier, F. (2014). Transient adult microbiota, gut homeostasis and longevity: novel insights from the Drosophila model. FEBS Lett, 588(22), 4250-4257. Filshie, B. K., Poulson, D. F., & Waterhouse, D. F. (1971). Ultrastructure of the copper-accumulating region of the Drosophila larval midgut. Tissue Cell, 3(1), 77-102. Gronke, S., Beller, M., Fellert, S., Ramakrishnan, H., Jackle, H., & Kuhnlein, R. P. (2003). Control of fat storage by a Drosophila PAT domain protein. Curr Biol, 13(7), 603-606. Gronke, S., Mildner, A., Fellert, S., Tennagels, N., Petry, S., Muller, G., . . . Kuhnlein, R. P. (2005). Brummer lipase is an evolutionary conserved fat storage regulator in Drosophila. Cell Metab, 1(5), 323-330. Guo, L., Karpac, J., Tran, S. L., & Jasper, H. (2014). PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan. Cell, 156(1-2), 109-122. Hardy, C. M., Birse, R. T., Wolf, M. J., Yu, L., Bodmer, R., & Gibbs, A. G. (2015). Obesity-associated cardiac dysfunction in starvation-selected Drosophila melanogaster. Am J Physiol Regul Integr Comp Physiol, 309(6), R658-667. Hughes, A. L., & Gottschling, D. E. (2012). An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast. Nature, 492(7428), 261-265. Kuhnlein, R. P. (2012). Thematic review series: Lipid droplet synthesis and metabolism: from yeast to man. Lipid droplet-based storage fat metabolism in Drosophila. J Lipid Res, 53(8), 1430-1436. Lee, K. P. (2015). Dietary protein:carbohydrate balance is a critical modulator of lifespan and reproduction in Drosophila melanogaster: A test using a chemically defined diet. J Insect Physiol, 75, 12-19. Lemaitre, B., & Miguel-Aliaga, I. (2013). The digestive tract of Drosophila melanogaster. Annu Rev Genet, 47, 377-404. Lim, D. H., Oh, C. T., Lee, L., Hong, J. S., Noh, S. H., Hwang, S., . . . Lee, Y. S. (2011). The endogenous siRNA pathway in Drosophila impacts stress resistance and lifespan by regulating metabolic homeostasis. FEBS Lett, 585(19), 3079-3085. Lin, W. S., Chen, J. Y., Wang, J. C., Chen, L. Y., Lin, C. H., Hsieh, T. R., . . . Wang, P. Y. (2014). The anti-aging effects of Ludwigia octovalvis on Drosophila melanogaster and SAMP8 mice. Age (Dordr), 36(2), 689-703. Lin, Y. J., Seroude, L., & Benzer, S. (1998). Extended life-span and stress resistance in the Drosophila mutant methuselah. Science, 282(5390), 943-946. Musselman, L. P., Fink, J. L., Narzinski, K., Ramachandran, P. V., Hathiramani, S. S., Cagan, R. L., & Baranski, T. J. (2011). A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila. Dis Model Mech, 4(6), 842-849. Na, J., Musselman, L. P., Pendse, J., Baranski, T. J., Bodmer, R., Ocorr, K., & Cagan, R. (2013). A Drosophila model of high sugar diet-induced cardiomyopathy. PLoS Genet, 9(1), e1003175. Naseer, M. I., Bibi, F., Alqahtani, M. H., Chaudhary, A. G., Azhar, E. I., Kamal, M. A., & Yasir, M. (2014). Role of gut microbiota in obesity, type 2 diabetes and Alzheimer's disease. CNS Neurol Disord Drug Targets, 13(2), 305-311. Neretti, N., Wang, P. Y., Brodsky, A. S., Nyguyen, H. H., White, K. P., Rogina, B., & Helfand, S. L. (2009). Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage. Proc Natl Acad Sci U S A, 106(7), 2277-2282. Phillips, M. D., & Thomas, G. H. (2006). Brush border spectrin is required for early endosome recycling in Drosophila. J Cell Sci, 119(Pt 7), 1361-1370. Pimentel, G. D., Micheletti, T. O., Pace, F., Rosa, J. C., Santos, R. V., & Lira, F. S. (2012). Gut-central nervous system axis is a target for nutritional therapies. Nutr J, 11, 22. Rajan, A., & Perrimon, N. (2013). Of flies and men: insights on organismal metabolism from fruit flies. BMC Biol, 11, 38. Reis, T., Van Gilst, M. R., & Hariharan, I. K. (2010). A Buoyancy-Based Screen of Drosophila Larvae for Fat-Storage Mutants Reveals a Role for <italic>Sir2</italic> in Coupling Fat Storage to Nutrient Availability. PLoS Genet, 6(11), e1001206. Rera, M., Clark, R. I., & Walker, D. W. (2012). Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proceedings of the National Academy of Sciences, 109(52), 21528-21533. Ridley, E. V., Wong, A. C., Westmiller, S., & Douglas, A. E. (2012). Impact of the resident microbiota on the nutritional phenotype of Drosophila melanogaster. PLoS One, 7(5), e36765. Rion, S., & Kawecki, T. J. (2007). Evolutionary biology of starvation resistance: what we have learned from Drosophila. J Evol Biol, 20(5), 1655-1664. Rose, M. R., Vu, L. N., Park, S. U., & Graves, J. L., Jr. (1992). Selection on stress resistance increases longevity in Drosophila melanogaster. Exp Gerontol, 27(2), 241-250. Royet, J. (2011). Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model Drosophila melanogaster. Cell Mol Life Sci, 68(22), 3651-3660. Sampson, T. R., & Mazmanian, S. K. (2015). Control of brain development, function, and behavior by the microbiome. Cell Host Microbe, 17(5), 565-576. Sanchez, D., Lopez-Arias, B., Torroja, L., Canal, I., Wang, X., Bastiani, M. J., & Ganfornina, M. D. (2006). Loss of glial lazarillo, a homolog of apolipoprotein D, reduces lifespan and stress resistance in Drosophila. Curr Biol, 16(7), 680-686. Sands, S. A., Tsau, S., Yankee, T. M., Parker, B. L., Ericsson, A. C., & LeVine, S. M. (2014). The effect of omeprazole on the development of experimental autoimmune encephalomyelitis in C57BL/6J and SJL/J mice. BMC Res Notes, 7, 605. Sommer, F., & Backhed, F. (2013). The gut microbiota--masters of host development and physiology. Nat Rev Microbiol, 11(4), 227-238. Song, Y. S. (2012). Vha16-1 regulates intestinal function and lifespan in Drosophila melanogaster. Master Thesis. Spugnini, E. P., Baldi, A., Buglioni, S., Carocci, F., de Bazzichini, G. M., Betti, G., . . . Fais, S. (2011). Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors. J Transl Med, 9, 221. Strasburger, M. (1932). Bau, Funktion und variabilitat des darmtractus von Drosophila melanogaster. Zeitschrift fur Wissenchaft Zoologie, 140, 539-649. Syu, Y. F., Huang, H. H., & Chen, C. Y. (2015). Do proton pump inhibitors contribute to weight gain? Obes Surg, 25(6), 1071-1072. Trinh, I., & Boulianne, G. L. (2013). Modeling obesity and its associated disorders in Drosophila. Physiology (Bethesda), 28(2), 117-124. Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), 1027-1031. Vavassori, S., & Mayer, A. (2014). A new life for an old pump: V-ATPase and neurotransmitter release. J Cell Biol, 205(1), 7-9. Vermeulen, C. J., & Loeschcke, V. (2007). Longevity and the stress response in Drosophila. Exp Gerontol, 42(3), 153-159. Viggiano, D., Ianiro, G., Vanella, G., Bibbo, S., Bruno, G., Simeone, G., & Mele, G. (2015). Gut barrier in health and disease: focus on childhood. Eur Rev Med Pharmacol Sci, 19(6), 1077-1085. Walker, D. W., Muffat, J., Rundel, C., & Benzer, S. (2006). Overexpression of a Drosophila homolog of apolipoprotein D leads to increased stress resistance and extended lifespan. Curr Biol, 16(7), 674-679. Wang, H. D., Kazemi-Esfarjani, P., & Benzer, S. (2004). Multiple-stress analysis for isolation of Drosophila longevity genes. Proc Natl Acad Sci U S A, 101(34), 12610-12615. Wang, L., Karpac, J., & Jasper, H. (2014). Promoting longevity by maintaining metabolic and proliferative homeostasis. J Exp Biol, 217(Pt 1), 109-118. Wang, P. Y., Neretti, N., Whitaker, R., Hosier, S., Chang, C., Lu, D., . . . Helfand, S. L. (2009). Long-lived Indy and calorie restriction interact to extend life span. Proc Natl Acad Sci U S A, 106(23), 9262-9267. Ward, E. K., Jensen-Otsu, E., Schoen, J. A., Rothchild, K., Mitchell, B., & Austin, G. L. (2015). Acid suppression medications are associated with suboptimal weight loss after laparoscopic Roux-en-Y gastric bypass in patients older than 40 years. Surg Obes Relat Dis, 11(3), 585-590. Ward, E. K., Schuster, D. P., Stowers, K. H., Royse, A. K., Ir, D., Robertson, C. E., . . . Austin, G. L. (2014). The effect of PPI use on human gut microbiota and weight loss in patients undergoing laparoscopic Roux-en-Y gastric bypass. Obes Surg, 24(9), 1567-1571. Williamson, W. R., Wang, D., Haberman, A. S., & Hiesinger, P. R. (2010). A dual function of V0-ATPase a1 provides an endolysosomal degradation mechanism in Drosophila melanogaster photoreceptors. J Cell Biol, 189(5), 885-899. Yoshikawa, I., Nagato, M., Yamasaki, M., Kume, K., & Otsuki, M. (2009). Long-term treatment with proton pump inhibitor is associated with undesired weight gain. World J Gastroenterol, 15(38), 4794-4798. Yu, L. C., Wang, J. T., Wei, S. C., & Ni, Y. H. (2012). Host-microbial interactions and regulation of intestinal epithelial barrier function: From physiology to pathology. World J Gastrointest Pathophysiol, 3(1), 27-43. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19538 | - |
dc.description.abstract | 老化與代謝症候群是當代醫學的重要課題,近年來果蠅廣被應用於這些問題的基礎研究。在先前的研究中,我們透過突變株篩選,發現消化道中酸分泌缺失的果蠅會出現類似代謝症候群的表現型(肥胖及高三酸甘油酯),且其壽命顯著縮短,顯示消化道酸鹼度可能影響老化與代謝過程。
為延續上述成果,本計畫繼續透過基因操弄與藥物介入等方式,建立消化道中段酸分泌異常的果蠅模式,進而系統性的探討消化道中段酸分泌不足對於老化與代謝的影響。在代謝表現型方面,我們發現腸道中段酸度不足的果蠅有體脂肪含量與體重上升,與飢餓耐受度增加等現象。在老化過程方面,我們發現這些果蠅的消化道障壁功能異常提早出現,壽命也顯著縮短。我們也在胃酸抑制的小鼠模式上觀察到類似的代謝表現型(肥胖及高脂血症),進一步印證了消化道中段酸度在代謝調控方面的角色。此外,我們的初步研究顯示果蠅腸道中段酸度會隨年齡下降,而卡路里節制可以減緩此情形,這暗示卡路里節制之所以能延長壽命,部分可能是透過維持腸道酸度而達成。期盼未來能夠藉由本研究所建立的動物模式,進一步釐清消化道酸鹼度與代謝及老化的關聯性。 | zh_TW |
dc.description.abstract | Previous work in our lab showed that Drosophila melanogaster harboring hypomorphic mutations in vha16-1 gene, which encodes vacuolar H+-ATPase subunit c and is highly expressed in middle midgut, exhibit reduced midgut acidification, as well as metabolic syndrome-like phenotypes (obesity, elevated triacylglycerol content), better starvation resistance, and a reduced lifespan. This observation led to the hypothesis that midgut acidity may be a regulator of systemic metabolism.
In this project, we established different fly models to test the hypothesis. We demonstrated that both genetic and pharmacological models of flies with deficient midgut acidification display increased triacylglycerol content and body weight, as well as a reduced lifespan. We also found that flies with deficient midgut acidification exhibit accelerated gut barrier dysfunction. Furthermore, our preliminary data showed that midgut acidity decreases with age in wild-type flies, and calorie restriction attenuates the age-dependent decline in midgut acidity. To explore whether the metabolic role of midgut acidity is conserved across species, we examined mice treated with proton pump inhibitor. These mice exhibited metabolic phenotypes reminiscent of flies with deficient midgut acidification, including reduced gastric juice acidity, increased serum triacylglycerol and cholesterol, and increased body weight gain. Taken together, our studies identified midgut acidity as a novel player in gut homeostasis and systemic metabolism. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:04:16Z (GMT). No. of bitstreams: 1 ntu-105-R01454012-1.pdf: 2212929 bytes, checksum: 8923cd9e224f5a37f92023b1e299b06f (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 口試委員會審定書………………………………………………………. i
誌謝………………………………………………………………………. ii 中文摘要……………………………………………………………........ iii 英文摘要……………………………………………………………........ iv 目錄……………………………………………………………................. v 圖目錄……………………………………................................................ vii 表目錄……………………………………............................................... viii Chapter 1: Introduction 1.1 Drosophila melanogaster as a model to study aging and metabolism……………………………………………..………..1 1.2 Acid secretion in Drosophila midgut.............................….............3 1.3 Deficient midgut acidification is associated with altered lipid metabolism and shortened lifespan in Drosophila........................4 Chapter 2: Materials and Methods 2.1 Flies……………………………………………………………….5 2.2 Body weight and triacylglycerol measurements………………….6 2.3 Determination of midgut acidity in adult flies………………........6 2.4 Fly lifespan assay……………………………………………........7 2.5 Gut barrier function in flies…………………………………........7 2.6 Mouse experiments……….....................……………………........8 2.7 Statistics……………………………………………………..........8 Chapter 3: Results 3.1 Genetic models of Drosophila melanogaster with deficient midgut acidification………………………………………............9 3.2 Pharmacological models of Drosophila melanogaster with deficient midgut acidification……………………………...........10 3.3 Effect of deficient midgut acidification on gut barrier function in flies……………………………..................................................12 3.4 Effect of calorie restriction on midgut acidity in flies..................13 3.5 Metabolic effects of stomach acid suppression in mice...............15 Chapter 4: Discussion 4.1 Drosophila models of deficient midgut acidification...................17 4.2 Interrelationships of lipid metabolism, body weight, starvation resistance, and lifespan..................................................................19 4.3 Gut homeostasis and aging and metabolism.................................21 4.4 Disease modeling and translational medicine...............................23 Chapter 5: Conclusion.................................................................................25 Bibliography……………………………………........................................26 Appendix 1: Schematic diagram of the midgut of adult Drosophila..........34 | |
dc.language.iso | en | |
dc.title | 以果蠅與小鼠模式探討胃酸對代謝與壽命之調控 | zh_TW |
dc.title | Midgut Acidity Regulates Metabolism and Lifespan in Drosophila melanogaster and Mice | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 詹智強,傅在峰 | |
dc.subject.keyword | 胃酸,代謝,肥胖,代謝症候群,老化,壽命, | zh_TW |
dc.subject.keyword | midgut acidity,metabolism,obesity,metabolic syndrome,aging,lifespan, | en |
dc.relation.page | 34 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2016-02-22 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 腦與心智科學研究所 | zh_TW |
顯示於系所單位: | 腦與心智科學研究所 |
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