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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳益群(Yi-Chun Wu) | |
| dc.contributor.author | Erh-Ya Lin | en |
| dc.contributor.author | 林爾雅 | zh_TW |
| dc.date.accessioned | 2023-03-19T21:29:55Z | - |
| dc.date.copyright | 2022-10-14 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-09-22 | |
| dc.identifier.citation | Abed Rabbo, M., Khodour, Y., Kaguni, L. S., & Stiban, J. (2021). Sphingolipid lysosomal storage diseases: from bench to bedside. Lipids in Health and Disease, 20(1), 1-29. Aguisanda, F., Thorne, N., & Zheng, W. (2017). Targeting Wolman disease and cholesteryl ester storage disease: disease pathogenesis and therapeutic development. Current chemical genomics and translational medicine, 11, 1. Alessenko, A. V., & Albi, E. (2020). Exploring sphingolipid implications in neurodegeneration. Frontiers in Neurology, 11, 437. Barrett, A., & Hermann, G. J. (2016). A Caenorhabditis elegans homologue of LYST functions in endosome and lysosome?related organelle biogenesis. Traffic, 17(5), 515-535. Breslow, D. K. (2013). Sphingolipid homeostasis in the endoplasmic reticulum and beyond. Cold Spring Harbor perspectives in biology, 5(4), a013326. Carlsson, E. R., Allin, K. H., Madsbad, S., & Fenger, M. (2019). Phosphatidylcholine and its relation to apolipoproteins A-1 and B changes after Roux-en-Y gastric bypass: a cohort study. Lipids in Health and Disease, 18(1), 1-11. Cheng, X., Jiang, X., Tam, K. Y., Li, G., Zheng, J., & Zhang, H. (2019). Sphingolipidomic analysis of C. elegans reveals development-and environment-dependent metabolic features. International journal of biological sciences, 15(13), 2897. Colombaioni, L., & Garcia-Gil, M. (2004). Sphingolipid metabolites in neural signalling and function. Brain research reviews, 46(3), 328-355. Du, H., Heur, M., Duanmu, M., Grabowski, G. A., Hui, D. Y., Witte, D. P., & Mishra, J. (2001). Lysosomal acid lipase-deficient mice: depletion of white and brown fat, severe hepatosplenomegaly, and shortened life span. Journal of lipid research, 42(4), 489-500. Dubland, J. A., & Francis, G. A. (2015). Lysosomal acid lipase: at the crossroads of normal and atherogenic cholesterol metabolism. Frontiers in cell and developmental biology, 3, 3. Fagone, P., & Jackowski, S. (2013). Phosphatidylcholine and the CDP–choline cycle. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1831(3), 523-532. Falomir-Lockhart, L. J., Cavazzutti, G. F., Gim?nez, E., & Toscani, A. M. (2019). Fatty acid signaling mechanisms in neural cells: fatty acid receptors. Frontiers in cellular neuroscience, 13, 162. Fogel, J. L., Thein, T. Z. T., & Mariani, F. V. (2012). Use of LysoTracker to detect programmed cell death in embryos and differentiating embryonic stem cells. JoVE (Journal of Visualized Experiments)(68), e4254. Gibellini, F., & Smith, T. K. (2010). The Kennedy pathway—de novo synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB life, 62(6), 414-428. Gomaraschi, M., Bonacina, F., & Norata, G. (2019). Lysosomal acid lipase: from cellular lipid handler to immunometabolic target. Trends in pharmacological sciences, 40(2), 104-115. Gorelik, A., Illes, K., Heinz, L. X., Superti-Furga, G., & Nagar, B. (2016). Crystal structure of mammalian acid sphingomyelinase. Nature communications, 7(1), 1-9. Griffin, B. A. (2013). Lipid metabolism. Surgery (Oxford), 31(6), 267-272. Guti?rrez, S., Svahn, S. L., & Johansson, M. E. (2019). Effects of omega-3 fatty acids on immune cells. International journal of molecular sciences, 20(20), 5028. Hannun, Y. A., & Obeid, L. M. (2008). Principles of bioactive lipid signalling: lessons from sphingolipids. Nature reviews Molecular cell biology, 9(2), 139-150. Hannun, Y. A., & Obeid, L. M. (2018). Sphingolipids and their metabolism in physiology and disease. Nature reviews Molecular cell biology, 19(3), 175-191. Hermann, G. J., Schroeder, L. K., Hieb, C. A., Kershner, A. M., Rabbitts, B. M., Fonarev, P., . . . Priess, J. R. (2005). Genetic analysis of lysosomal trafficking in Caenorhabditis elegans. Molecular biology of the cell, 16(7), 3273-3288. Huizing, M., Helip-Wooley, A., Westbroek, W., Gunay-Aygun, M., & Gahl, W. A. (2008). Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annual review of genomics and human genetics, 9, 359. Jackson, K. G., Maitin, V., Leake, D. S., Yaqoob, P., & Williams, C. M. (2006). Saturated fat-induced changes in Sf 60–400 particle composition reduces uptake of LDL by HepG2 cells. Journal of lipid research, 47(2), 393-403. Jones, K. T., & Ashrafi, K. (2009). Caenorhabditis elegans as an emerging model for studying the basic biology of obesity. Disease models & mechanisms, 2(5-6), 224-229. Kaletta, T., & Hengartner, M. O. (2006). Finding function in novel targets: C. elegans as a model organism. Nature reviews Drug discovery, 5(5), 387-399. Kelekar, A. (2006). Autophagy. Annals of the New York Academy of Sciences, 1066(1), 259-271. Kim, Y., & Sun, H. (2012). ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target. Kolter, T., & Sandhoff, K. (2006). Sphingolipid metabolism diseases. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1758(12), 2057-2079. Kornhuber, J., Rhein, C., M?ller, C. P., & M?hle, C. (2015). Secretory sphingomyelinase in health and disease. Biological chemistry, 396(6-7), 707-736. Koyiloth, M., & Gummadi, S. N. (2022). Regulation and functions of membrane lipids: Insights from Caenorhabditis elegans. BBA Advances, 100043. Lass, A., Zimmermann, R., Oberer, M., & Zechner, R. (2011). Lipolysis–a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Progress in lipid research, 50(1), 14-27. Lemieux, G. A., & Ashrafi, K. (2015). Insights and challenges in using C. elegans for investigation of fat metabolism. Critical Reviews in Biochemistry and Molecular Biology, 50(1), 69-84. Li, F., & Zhang, H. (2019). Lysosomal acid lipase in lipid metabolism and beyond. Arteriosclerosis, thrombosis, and vascular biology, 39(5), 850-856. Li, Z., & Vance, D. E. (2008). Thematic review series: glycerolipids. Phosphatidylcholine and choline homeostasis. Journal of lipid research, 49(6), 1187-1194. Lim, C.-Y., & Zoncu, R. (2016). The lysosome as a command-and-control center for cellular metabolism. Journal of Cell Biology, 214(6), 653-664. Liu, Y., Samuel, B. S., Breen, P. C., & Ruvkun, G. (2014). Caenorhabditis elegans pathways that surveil and defend mitochondria. Nature, 508(7496), 406-410. MacNeil, L. T., Watson, E., Arda, H. E., Zhu, L. J., & Walhout, A. J. (2013). Diet-induced developmental acceleration independent of TOR and insulin in C. elegans. Cell, 153(1), 240-252. 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. Journal of lipid research, 53(1), 28-33. Maria, P., & Evagelia, S. (2009). Obesity disease. Health Science Journal, 3(3), 132-138. Marza, E., Simonsen, K. T., F?rgeman, N. J., & Lesa, G. M. (2009). Expression of ceramide glucosyltransferases, which are essential for glycosphingolipid synthesis, is only required in a small subset of C. elegans cells. Journal of cell science, 122(6), 822-833. Mayer, J., & Thomas, D. W. (1967). Regulation of Food Intake and Obesity: The regulation of food intake is complex; a number of abnormalities may cause obesity. Science, 156(3773), 328-337. Merrill, A. H. (2002). De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway. Journal of Biological Chemistry, 277(29), 25843-25846. Morris, C., Foster, O. K., Handa, S., Peloza, K., Voss, L., Somhegyi, H., . . . Hermann, G. J. (2018). Function and regulation of the Caenorhabditis elegans Rab32 family member GLO-1 in lysosome-related organelle biogenesis. PLoS Genet, 14(11), e1007772. doi:10.1371/journal.pgen.1007772 O’Rourke, E. J., & Ruvkun, G. (2013). MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to nutrient availability. Nature cell biology, 15(6), 668-676. Papackova, Z., & Cahova, M. (2015). Fatty acid signaling: the new function of intracellular lipases. International journal of molecular sciences, 16(2), 3831-3855. Pitt, J. J. (2009). Principles and applications of liquid chromatography-mass spectrometry in clinical biochemistry. The Clinical Biochemist Reviews, 30(1), 19. Pralhada Rao, R., Vaidyanathan, N., Rengasamy, M., Mammen Oommen, A., Somaiya, N., & Jagannath, M. (2013). Sphingolipid metabolic pathway: an overview of major roles played in human diseases. Journal of lipids, 2013. Roberti, M. J., Lopez, L. O., Ossato, G., Steinmetz, I., Haas, P., Hecht, F., & Alvarez, L. A. (2020). TauSense: a fluorescence lifetime-based tool set for everyday imaging. Nat. Methods. Roh, H. C., Collier, S., Guthrie, J., Robertson, J. D., & Kornfeld, K. (2012). Lysosome-related organelles in intestinal cells are a zinc storage site in C. elegans. Cell metabolism, 15(1), 88-99. Singh, A., & Del Poeta, M. (2016). Sphingolipidomics: an important mechanistic tool for studying fungal pathogens. Frontiers in microbiology, 7, 501. Singh, R. (2011). Autophagy and regulation of lipid metabolism. Sensory and Metabolic Control of Energy Balance, 35-46. Sun-Wada, G.-H., Wada, Y., & Futai, M. (2003). Lysosome and lysosome-related organelles responsible for specialized functions in higher organisms, with special emphasis on vacuolar-type proton ATPase. Cell structure and function, 28(5), 455-463. Swanson, D., Block, R., & Mousa, S. A. (2012). Omega-3 fatty acids EPA and DHA: health benefits throughout life. Advances in nutrition, 3(1), 1-7. Touchstone, J. C. (1995). Thin-layer chromatographic procedures for lipid separation. Journal of Chromatography B: Biomedical Sciences and Applications, 671(1-2), 169-195. van der Veen, J. N., Kennelly, J. P., Wan, S., Vance, J. E., Vance, D. E., & Jacobs, R. L. (2017). The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1859(9), 1558-1572. Ward, D., Shiflett, S. L., & Kaplan, J. (2002). Chediak-Higashi syndrome: a clinical and molecular view of a rare lysosomal storage disorder. Current molecular medicine, 2(5), 469-477. Watts, J. L. (2009). Fat synthesis and adiposity regulation in Caenorhabditis elegans. Trends in Endocrinology & Metabolism, 20(2), 58-65. Witting, M., & Schmitt-Kopplin, P. (2016). The Caenorhabditis elegans lipidome: A primer for lipid analysis in Caenorhabditis elegans. Archives of biochemistry and biophysics, 589, 27-37. Zechner, R., Madeo, F., & Kratky, D. (2017). Cytosolic lipolysis and lipophagy: two sides of the same coin. Nature reviews Molecular cell biology, 18(11), 671-684. Zhang, H. (2018). Lysosomal acid lipase and lipid metabolism: new mechanisms, new questions, and new therapies. Current opinion in lipidology, 29(3), 218. Zheng, J., & Greenway, F. (2012). Caenorhabditis elegans as a model for obesity research. International journal of obesity, 36(2), 186-194. Zhitomirsky, B., Farber, H., & Assaraf, Y. G. (2018). LysoTracker and MitoTracker Red are transport substrates of P?glycoprotein: implications for anticancer drug design evading multidrug resistance. Journal of Cellular and Molecular Medicine, 22(4), 2131-2141. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84057 | - |
| dc.description.abstract | 飲食提供生物體營養及能量。多餘的能量會被儲存成脂質且脂質恆定不平衡會造成脂肪累積導致代謝疾病。因此，了解飲食如何影響生物體中的脂質代謝就顯得重要。類溶?體相關胞器(LRO)是一種和溶?體有許多相似特徵的酸性胞器並被發現存在於秀麗隱桿線蟲到人類等生物體中。然而，它的功能尚不明確。在本篇研究中，我們探討了線蟲中的類溶?體相關胞器如何透過不同的細菌飲食-OP50及DA1877影響脂質代謝。我們發現在位於酸性胞器中的一個酸性脂肪?在不同飲食中mRNA表現量有顯著的改變。除此之外，我們證明了在DA飲食下該脂肪?參與在類溶?體相關胞器數量、磷脂醯膽鹼及三酸甘油脂的表現量的調控。另一方面，鞘脂的代謝產物參與在磷脂醯膽鹼的合成中，我們也發現飲食會影響到鞘脂的含量。而鞘脂的恆定在DA飲食的線蟲中至關重要，可能是由於它參與磷脂醯膽鹼的合成。我的研究揭示了從類溶?體相關胞器到磷脂醯膽鹼和脂質代謝的信號通路，並將提供飲食對慢性疾病（如肥胖）的病因和預防的見解。 | zh_TW |
| dc.description.abstract | Diets provide nutrients and energy for organisms. Excessive energy would be stored as lipid and Imbalanced lipid homeostasis causing fat accumulation would lead to metabolic disorders. Therefore, understanding how diets regulate organismal lipid metabolism is important. Lysosome-related organelle(LRO) is an acidic organelle which shares many features with the lysosome and is found from C. elegans to human. However, their functions are not well characterized. In this work, we examined how LROs influence lipid metabolism in C. elegans by different bacterial diets, OP50 and DA1877. We found a specific acid lipase, which is localized to acidic organelles, showed a significant change at the mRNA level in response to different diets. Furthermore, we demonstrated that the acid lipase is involved in the regulation of LRO number and triacylglycerol level in response to DA diet. Interestingly, the results of lipidomics profiling showed that this lipase is required to promote the phosphatidylcholine level in the DA diet. On the other hand, we also found that the two bacterial diets affect sphingolipid metabolism, possibly due to its involvement in PC synthesis. My work reveals a novel signaling pathway from LRO to PC and lipid metabolism, and would provide insights into the dietary implication in the cause and prevention of chronic diseases, such as obesity. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T21:29:55Z (GMT). No. of bitstreams: 1 U0001-2209202217492800.pdf: 3373855 bytes, checksum: 12750aec07d49db121d82bb962278e3e (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 致謝 i 摘要 ii Abstract iii Introduction 1 Diet is crucial for organisms 1 Lipid metabolism 1 Phosphatidylcholine synthesis 2 Sphingolipids 3 Lysosome related organelle 5 Lysosomal acid lipase 7 C. elegans is a great model organism for studying lipid metabolism 8 Materials and Methods 10 Caenorhabditis elegans strains 10 Construction and microinjection 10 Bacteria strain and Culture Conditions 12 Worm synchronization 12 Oil Red O staining and quantification 13 RNA extraction and real-time PCR 13 LysoTracker staining and quantification 14 Fluorescence imaging 15 Lipid extraction 16 Thin-layer chromatogram 18 LC-MS and LC-MS/MS 19 Statistics analysis 19 Results 21 TauGating is a useful technique to filter out autofluorescence 21 LysoTracker stains GLO-1(+) organelles 21 LIPL-2 is involved in LROs biogenesis and lipid metabolism 22 LIPL-2 regulates lipid content through phosphatidylcholine 24 Sphingolipid analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) 26 The levels of ceramides and sphingomyelins did not change in the worms fed by different diets 27 ASM-3 increased sphingolipids level on DA diet 28 Discussion 31 LysoTracker staining and GLO-1::GFP(+) organelles’ acidity 31 LIPL-2 and specific fatty acids 31 The activation of ASM-3 32 Various sphingolipids regulation and ASM-3 function 33 Figures 35 Figure 1. Tau gating separates different fluorescent signals depend on different lifetimes 36 Figure 2. LysoTracker stains GLO-1(+) organelles 38 Figure 3. lipl-2 transcripts were increased in DA-fed worms, and lipl-2 was involved in lipid metabolism and LROs biogenesis 41 Figure 4. lipl -2 mutants decreased phosphatidylcholine level 44 Figure 5. Sphingolipid analysis by LC-MS/MS 47 Figure 6. The levels of ceramides, sphingomyelins and sphingosine in wild type worms fed by different diets 50 Figure 7 Ceramides and sphingomyelins increased in asm-3mutant worms fed on DA diet 54 Supplementary figures 57 Supplementary figure 1 57 Supplementary figure 2 57 Supplementary figure 3 58 Supplementary figure 4 59 Supplementary figure 5 60 Supplementary figure 6 61 Supplementary figure 7 62 Supplementary figure 8 62 Supplementary figure 9 63 Supplementary figure 10 64 Supplementary figure 11 65 Supplementary figure 12 66 Supplementary figure 13 67 Supplementary figure 14 68 Supplementary figure 15 68 Supplementary figure 16 69 Supplementary figure 17 70 Table 1 71 Table 2 73 Table 3: primers for qRT-PCR 73 Table 4: primers for Plipl-2::lipl-2::mCherry construct 73 References 74 | |
| dc.language.iso | en | |
| dc.subject | 秀麗隱桿線蟲 | zh_TW |
| dc.subject | 飲食 | zh_TW |
| dc.subject | 類溶?體相關胞器 | zh_TW |
| dc.subject | 脂質代謝 | zh_TW |
| dc.subject | 鞘脂 | zh_TW |
| dc.subject | diet | en |
| dc.subject | Caenorhabditis elegans | en |
| dc.subject | sphingolipid | en |
| dc.subject | lipid metabolism | en |
| dc.subject | lysosome related organelle | en |
| dc.title | 線蟲內由不同飲食調控的脂質代謝 | zh_TW |
| dc.title | C. elegans lipid metabolism mediated by different bacterial diets | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 廖秀娟(Hsiu-Chuan Liao),王昭雯(Chao-Wen Wang) | |
| dc.subject.keyword | 飲食,類溶?體相關胞器,脂質代謝,鞘脂,秀麗隱桿線蟲, | zh_TW |
| dc.subject.keyword | diet,lysosome related organelle,lipid metabolism,sphingolipid,Caenorhabditis elegans, | en |
| dc.relation.page | 78 | |
| dc.identifier.doi | 10.6342/NTU202203840 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2022-09-26 | |
| 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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