請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65416
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王培育(Pei-Yu Wang) | |
dc.contributor.author | Shang-Po Yang | en |
dc.contributor.author | 楊尚博 | zh_TW |
dc.date.accessioned | 2021-06-16T23:41:39Z | - |
dc.date.available | 2025-03-13 | |
dc.date.copyright | 2020-03-13 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-02-19 | |
dc.identifier.citation | 1. Alves-Bezerra, M., and Cohen, D.E. (2017). Triglyceride Metabolism in the Liver. Compr Physiol 8, 1-8.
2. Armstrong, L.E., Maughan, R.J., Senay, L.C., and Shirreffs, S.M. (2013). Limitations to the use of plasma osmolality as a hydration biomarker. Am J Clin Nutr 98, 503-504. 3. Bergeron, M.J., Clemencon, B., Hediger, M.A., and Markovich, D. (2013). SLC13 family of Na(+)-coupled di- and tri-carboxylate/sulfate transporters. Mol Aspects Med 34, 299-312. 4. Birkenfeld, A.L., Lee, H.Y., Guebre-Egziabher, F., Alves, T.C., Jurczak, M.J., Jornayvaz, F.R., Zhang, D., Hsiao, J.J., Martin-Montalvo, A., Fischer-Rosinsky, A., et al. (2011). Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice. Cell Metab 14, 184-195. 5. Birkenfeld, A.L., and Shulman, G.I. (2014). Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes. Hepatology 59, 713-723. 6. Bobulescu, I.A. (2010). Renal lipid metabolism and lipotoxicity. Curr Opin Nephrol Hypertens 19, 393-402. 7. Brachs, S., Winkel, A.F., Tang, H., Birkenfeld, A.L., Brunner, B., Jahn-Hofmann, K., Margerie, D., Ruetten, H., Schmoll, D., and Spranger, J. (2016). Inhibition of citrate cotransporter Slc13a5/mINDY by RNAi improves hepatic insulin sensitivity and prevents diet-induced non-alcoholic fatty liver disease in mice. Mol Metab 5, 1072-1082. 8. Browning, J.D., Szczepaniak, L.S., Dobbins, R., Nuremberg, P., Horton, J.D., Cohen, J.C., Grundy, S.M., and Hobbs, H.H. (2004). Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40, 1387-1395. 9. Burn, S.F. (2012). Detection of β-Galactosidase Activity: X-gal Staining. In Kidney Development: Methods and Protocols, O. Michos, ed. (Totowa, NJ: Humana Press), pp. 241-250. 10. Can, A., Dao, D.T., Arad, M., Terrillion, C.E., Piantadosi, S.C., and Gould, T.D. (2012a). The mouse forced swim test. J Vis Exp, e3638. 11. Can, A., Dao, D.T., Terrillion, C.E., Piantadosi, S.C., Bhat, S., and Gould, T.D. (2012b). The tail suspension test. J Vis Exp, e3769. 12. Chen, X., Tsukaguchi, H., Chen, X.Z., Berger, U.V., and Hediger, M.A. (1999). Molecular and functional analysis of SDCT2, a novel rat sodium-dependent dicarboxylate transporter. J Clin Invest 103, 1159-1168. 13. Ciarimboli, G., Lancaster, C.S., Schlatter, E., Franke, R.M., Sprowl, J.A., Pavenstadt, H., Massmann, V., Guckel, D., Mathijssen, R.H., Yang, W., et al. (2012). Proximal tubular secretion of creatinine by organic cation transporter OCT2 in cancer patients. Clin Cancer Res 18, 1101-1108. 14. Fujita, T., Katsukawa, H., Yodoya, E., Wada, M., Shimada, A., Okada, N., Yamamoto, A., and Ganapathy, V. (2005). Transport characteristics of N-acetyl-L-aspartate in rat astrocytes: involvement of sodium-coupled high-affinity carboxylate transporter NaC3/NaDC3-mediated transport system. J Neurochem 93, 706-714. 15. George, R.L., Huang, W., Naggar, H.A., Smith, S.B., and Ganapathy, V. (2004). Transport of N-acetylaspartate via murine sodium/dicarboxylate cotransporter NaDC3 and expression of this transporter and aspartoacylase II in ocular tissues in mouse. Biochim Biophys Acta 1690, 63-69. 16. Hardies, K., de Kovel, C.G., Weckhuysen, S., Asselbergh, B., Geuens, T., Deconinck, T., Azmi, A., May, P., Brilstra, E., Becker, F., et al. (2015). Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain 138, 3238-3250. 17. He, J., Pan, H., Liang, W., Xiao, D., Chen, X., Guo, M., and He, J. (2017). Prognostic Effect of Albumin-to-Globulin Ratio in Patients with solid tumors: A Systematic Review and Meta-analysis. Journal of Cancer 8, 4002-4010. 18. Huang, L., Scarpellini, A., Funck, M., Verderio, E.A., and Johnson, T.S. (2013). Development of a chronic kidney disease model in C57BL/6 mice with relevance to human pathology. Nephron Extra 3, 12-29. 19. Huang, W., Wang, H., Kekuda, R., Fei, Y.J., Friedrich, A., Wang, J., Conway, S.J., Cameron, R.S., Leibach, F.H., and Ganapathy, V. (2000). Transport of N-acetylaspartate by the Na(+)-dependent high-affinity dicarboxylate transporter NaDC3 and its relevance to the expression of the transporter in the brain. J Pharmacol Exp Ther 295, 392-403. 20. Hur, Y.N., Hong, G.H., Choi, S.H., Shin, K.H., and Chun, B.G. (2010). High fat diet altered the mechanism of energy homeostasis induced by nicotine and withdrawal in C57BL/6 mice. Mol Cells 30, 219-226. 21. Inoue, K., Fei, Y.J., Huang, W., Zhuang, L., Chen, Z., and Ganapathy, V. (2002a). Functional identity of Drosophila melanogaster Indy as a cation-independent, electroneutral transporter for tricarboxylic acid-cycle intermediates. Biochem J 367, 313-319. 22. Inoue, K., Zhuang, L., and Ganapathy, V. (2002b). Human Na+ -coupled citrate transporter: primary structure, genomic organization, and transport function. Biochem Biophys Res Commun 299, 465-471. 23. Inoue, K., Zhuang, L., Maddox, D.M., Smith, S.B., and Ganapathy, V. (2002c). Structure, function, and expression pattern of a novel sodium-coupled citrate transporter (NaCT) cloned from mammalian brain. J Biol Chem 277, 39469-39476. 24. Kaidanovich-Beilin, O., Lipina, T., Vukobradovic, I., Roder, J., and Woodgett, J.R. (2011). Assessment of social interaction behaviors. J Vis Exp. 25. Kaufhold, M., Schulz, K., Breljak, D., Gupta, S., Henjakovic, M., Krick, W., Hagos, Y., Sabolic, I., Burckhardt, B.C., and Burckhardt, G. (2011). Differential interaction of dicarboxylates with human sodium-dicarboxylate cotransporter 3 and organic anion transporters 1 and 3. Am J Physiol Renal Physiol 301, F1026-1034. 26. Kekuda, R., Wang, H., Huang, W., Pajor, A.M., Leibach, F.H., Devoe, L.D., Prasad, P.D., and Ganapathy, V. (1999). Primary structure and functional characteristics of a mammalian sodium-coupled high affinity dicarboxylate transporter. J Biol Chem 274, 3422-3429. 27. Knauf, F., Mohebbi, N., Teichert, C., Herold, D., Rogina, B., Helfand, S., Gollasch, M., Luft, F.C., and Aronson, P.S. (2006). The life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates. Biochem J 397, 25-29. 28. Knauf, F., Rogina, B., Jiang, Z., Aronson, P.S., and Helfand, S.L. (2002). Functional characterization and immunolocalization of the transporter encoded by the life-extending gene Indy. Proc Natl Acad Sci U S A 99, 14315-14319. 29. Kokko, J.P. (1972). Urea transport in proximal tubule and the descending limb of Henle. J Clin Invest 51, 1999-2008. 30. Liu, W., Hong, Q., Bai, X.Y., Fu, B., Xie, Y., Zhang, X., Li, J., Shi, S., Lv, Y., Sun, X., et al. (2010). High-affinity Na(+)-dependent dicarboxylate cotransporter promotes cellular senescence by inhibiting SIRT1. Mech Ageing Dev 131, 601-613. 31. Lueptow, L.M. (2017). Novel Object Recognition Test for the Investigation of Learning and Memory in Mice. J Vis Exp. 32. Ma, Y., Bai, X.Y., Du, X., Fu, B., and Chen, X. (2016). NaDC3 Induces Premature Cellular Senescence by Promoting Transport of Krebs Cycle Intermediates, Increasing NADH, and Exacerbating Oxidative Damage. J Gerontol A Biol Sci Med Sci 71, 1-12. 33. Moffett, J.R., Ross, B., Arun, P., Madhavarao, C.N., and Namboodiri, A.M. (2007). N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol 81, 89-131. 34. Neretti, N., Wang, P.Y., Brodsky, A.S., Nyguyen, H.H., White, K.P., Rogina, B., and 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, 2277-2282. 35. Otto, G.P., Rathkolb, B., Oestereicher, M.A., Lengger, C.J., Moerth, C., Micklich, K., Fuchs, H., Gailus-Durner, V., Wolf, E., and Hrabe de Angelis, M. (2016). Clinical Chemistry Reference Intervals for C57BL/6J, C57BL/6N, and C3HeB/FeJ Mice (Mus musculus). J Am Assoc Lab Anim Sci 55, 375-386. 36. Pajor, A.M. (2014). Sodium-coupled dicarboxylate and citrate transporters from the SLC13 family. Pflugers Arch 466, 119-130. 37. Pajor, A.M., Gangula, R., and Yao, X. (2001). Cloning and functional characterization of a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain. Am J Physiol Cell Physiol 280, C1215-1223. 38. Rogers, R.P., and Rogina, B. (2014). Increased mitochondrial biogenesis preserves intestinal stem cell homeostasis and contributes to longevity in Indy mutant flies. Aging (Albany NY) 6, 335-350. 39. Rogers, R.P., and Rogina, B. (2015). The role of INDY in metabolism, health and longevity. Front Genet 6, 204. 40. Rogina, B., Reenan, R.A., Nilsen, S.P., and Helfand, S.L. (2000). Extended life-span conferred by cotransporter gene mutations in Drosophila. Science 290, 2137-2140. 41. Schlessinger, A., Sun, N.N., Colas, C., and Pajor, A.M. (2014). Determinants of substrate and cation transport in the human Na+/dicarboxylate cotransporter NaDC3. J Biol Chem 289, 16998-17008. 42. Seibenhener, M.L., and Wooten, M.C. (2015). Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp, e52434. 43. Smith, G.S., Walter, G.L., and Walker, R.M. (2013). Clinical Pathology in Non-Clinical Toxicology Testing. 565-594. 44. Strungaru, M.H., Footz, T., Liu, Y., Berry, F.B., Belleau, P., Semina, E.V., Raymond, V., and Walter, M.A. (2011). PITX2 is involved in stress response in cultured human trabecular meshwork cells through regulation of SLC13A3. Invest Ophthalmol Vis Sci 52, 7625-7633. 45. Suh, B., Park, S., Shin, D.W., Yun, J.M., Keam, B., Yang, H.K., Ahn, E., Lee, H., Park, J.H., and Cho, B. (2014). Low albumin-to-globulin ratio associated with cancer incidence and mortality in generally healthy adults. Ann Oncol 25, 2260-2266. 46. Thevenon, J., Milh, M., Feillet, F., St-Onge, J., Duffourd, Y., Juge, C., Roubertie, A., Heron, D., Mignot, C., Raffo, E., et al. (2014). Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life. Am J Hum Genet 95, 113-120. 47. Wada, M., Shimada, A., and Fujita, T. (2006). Functional characterization of Na+ -coupled citrate transporter NaC2/NaCT expressed in primary cultures of neurons from mouse cerebral cortex. Brain Res 1081, 92-100. 48. Walf, A.A., and Frye, C.A. (2007). The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2, 322-328. 49. Wang, H., Fei, Y.J., Kekuda, R., Yang-Feng, T.L., Devoe, L.D., Leibach, F.H., Prasad, P.D., and Ganapathy, V. (2000). Structure, function, and genomic organization of human Na(+)-dependent high-affinity dicarboxylate transporter. Am J Physiol Cell Physiol 278, C1019-1030. 50. Wang, J.Z., Chen, X.M., Zhu, H.Y., Peng, L.X., and Hong, Q. (2003). Relationship between aging and renal high-affinity sodium-dependent dicarboxylate cotransporter-3 expression characterized with antifusion protein antibody. J Gerontol a-Biol 58, 879-888. 51. Wang, P.Y., Neretti, N., Whitaker, R., Hosier, S., Chang, C., Lu, D., Rogina, B., and Helfand, S.L. (2009). Long-lived Indy and calorie restriction interact to extend life span. Proc Natl Acad Sci U S A 106, 9262-9267. 52. Weir, J.B. (1949). New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 109, 1-9. 53. Willmes, D.M., and Birkenfeld, A.L. (2013). The Role of INDY in Metabolic Regulation. Comput Struct Biotechnol J 6, e201303020. 54. Yang, M., and Crawley, J.N. (2009). Simple behavioral assessment of mouse olfaction. Curr Protoc Neurosci Chapter 8, Unit 8 24. 55. Yodoya, E., Wada, M., Shimada, A., Katsukawa, H., Okada, N., Yamamoto, A., Ganapathy, V., and Fujita, T. (2006). Functional and molecular identification of sodium-coupled dicarboxylate transporters in rat primary cultured cerebrocortical astrocytes and neurons. J Neurochem 97, 162-173. 56. Zaias, J., Mineau, M., Cray, C., Yoon, D., and Altman, N.H. (2009). Reference values for serum proteins of common laboratory rodent strains. J Am Assoc Lab Anim Sci 48, 387-390. 57. Zou, J., Wang, W., Pan, Y.W., Lu, S., and Xia, Z. (2015). Methods to measure olfactory behavior in mice. Curr Protoc Toxicol 63, 11 18 11-21. 58. Zwart, R., Peeva, P.M., Rong, J.X., and Sher, E. (2015). Electrophysiological characterization of human and mouse sodium-dependent citrate transporters (NaCT/SLC13A5) reveal species differences with respect to substrate sensitivity and cation dependence. J Pharmacol Exp Ther 355, 247-254. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65416 | - |
dc.description.abstract | 果蠅的長壽基因I’m Not Dead Yet (INDY)和哺乳動物裡的其中一個同源基因Solute carrier family 13, member 5 (SLC13A5)會轉譯出位於細胞膜上的二羧酸與三羧酸通道蛋白。這兩個基因已被科學家進行多次研究,發現這兩個基因的缺失會影響脂肪代謝、胰島素的訊息傳遞、能量的平衡、和肥胖。然而,另一個INDY在哺乳動物的同源基因Solute carrier family 13, member 3 (SLC13A3)雖然能夠運送較多種三羧酸循環中的中間產物,過去卻沒有研究針對此基因在腦功能和代謝上的影響。在我的研究中,我會藉由比較野生型老鼠(wild type mice)和SLC13A3剔除的老鼠(SLC13A3 knockout mice) 來觀察兩者在認知功能和代謝上的差異。我發現在老鼠身上剃除SLC13A3會降低牠們的體重,這可能是因為此基因的剃除會促進牠們能量的使用、減少身上脂肪的堆積,和降低肝臟中脂肪的合成。但是,我沒有發現到基因剃除會影響腦和腎臟的功能。這些結果顯示出SLC13A3能夠作為一個很好的研究對象來研究脂肪代謝機制,也可能在未來提供了具有潛力的策略來治療肥胖和非酒精性脂肪肝疾病。 | zh_TW |
dc.description.abstract | The life-extending gene I’m Not Dead Yet (INDY) in Drosophila and one of its mammalian homologs called Solute carrier family 13, member 5 (SLC13A5) encode di- and tri-carboxylate transporters on the plasma membrane and they have been highly investigated previously. Dysfunction of these genes would influence lipid metabolism, insulin signaling, energy balancing, brain, and obesity. However, another mammalian homolog of INDY called Solute carrier family 13, member 3 (SLC13A3), which could transport a wide range of intermediates in tricarboxylate cycle, has not been highly investigated for their functions on brain and metabolism. In this study, we compared SLC13A3 knockout mice with wild type mice to evaluate the changes in metabolism and brain functions. We found that the loss of SLC13A3 in mice could reduce their body weight. This may be due to their increased energy expenditure, the reduced accumulation of lipid, and the downregulation of the lipogenesis genes in the liver. However, the loss of SLC13A3 did not affect the normal function of brain and the kidney. These results show that SLC13A3 may be a great target for scientists to investigate the detailed mechanism of lipid metabolism and it might provide a potential way for the treatment of obesity and non-alcoholic fatty liver disease (NAFLD) in the future. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T23:41:39Z (GMT). No. of bitstreams: 1 ntu-109-R05454014-1.pdf: 5387565 bytes, checksum: dcb9f53a59cc6d33da6648ec5bafecc6 (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 口試委員審定書 i
誌謝 ii 中文摘要 iii Abstract iv Contents v Abbreviation table vii Chapter 1 Introduction 1 Chapter 2 Materials and Methods 5 2.1 Mice 5 2.2 Genotyping 5 2.3 Body weight monitoring and body composition analysis 7 2.4 Behavioral tests 7 2.5 Metabolic monitoring, food intake, and water intake 11 2.6 Biochemical analysis 12 2.7 Glucose tolerance test, insulin tolerance test, pyruvate tolerance test, and insulin concentration analysis 15 2.8 X-gal staining 16 2.9 RNA extraction and quantitative real-time PCR 17 2.10 Statistical analysis 18 Chapter 3 Results 19 3.1 Generation of SLC13A3 knockout mice 19 3.2 Di-/tri-carboxylates accumulated in SLC13A3-/- mice 20 3.3 Reduced body weight and higher energy expenditure in SLC13A3-/- mice 20 3.4 The motor performances and anxiety levels were not mediated by SLC13A3 21 3.5 The memory functions and the depression levels didn’t change after loss of SLC13A3 in mice 22 3.6 The olfactory functions were not affected by the loss of SLC13A3 23 3.7 Biochemical analysis revealed better lipid profile and normal functions in kidney and liver in SLC13A3-/- mice 23 3.8 The loss of SLC13A3 improved lipid metabolism and insulin sensitivity 24 Chapter 4 Discussion 26 Chapter 5 Table and Figures 31 Chapter 6 Reference 50 | |
dc.language.iso | en | |
dc.title | SLC13A3的缺失影響了老鼠的脂肪代謝而非認知功能 | zh_TW |
dc.title | Loss of SLC13A3 influences the lipid metabolism of mice
but not their cognitive functions | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 范守仁(Shou-Zen Fan),李宜釗(Yi-Chao Lee) | |
dc.subject.keyword | SLC13A3,脂肪代謝,肝臟,腦,認知功能,肥胖, | zh_TW |
dc.subject.keyword | SLC13A3,lipid metabolism,liver,brain,cognitive function,obesity, | en |
dc.relation.page | 53 | |
dc.identifier.doi | 10.6342/NTU201901576 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-02-19 | |
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 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-109-1.pdf 目前未授權公開取用 | 5.26 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。