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  1. NTU Theses and Dissertations Repository
  2. 醫學院
  3. 國際三校農業生技與健康醫療碩士學位學程
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/104588
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dc.contributor.advisor劉嚞睿zh_TW
dc.contributor.advisorJe-Ruei Liuen
dc.contributor.author沈冠妮zh_TW
dc.contributor.authorKuan-Ni Shenen
dc.date.accessioned2026-08-28T16:33:02Z-
dc.date.available2026-08-29-
dc.date.copyright2026-08-28-
dc.date.issued2026-
dc.date.submitted2026-07-15 00:00:00-
dc.identifier.citationFlori, L., Galgani, G., Bray, G., Ippolito, C., Segnani, C., Pellegrini, C., Citi, V., Bernardini, N., Martelli, A., & Calderone, V. (2025). Development of an adipocyte differentiation protocol using 3T3-L1 cells for the investigation of the browning process: Identification of the PPAR-γ agonist rosiglitazone as a browning reference drug. Frontiers in Pharmacology, 16, 1546456. https://doi.org/10.3389/fphar.2025.1546456

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Lancaster, G. I., Langley, K. G., Berglund, N. A., Kammoun, H. L., Reibe, S., Estevez, E., Weir, J., Mellett, N. A., Pernes, G., Conway, J. R. W., Lee, M. K. S., Timpson, P., Murphy, A. J., Masters, S. L., Gerondakis, S., Bartonicek, N., Kaczorowski, D. C., Dinger, M. E., Meikle, P. J., ... Febbraio, M. A. (2018). Evidence that TLR4 is not a receptor for saturated fatty acids but mediates lipid-induced inflammation by reprogramming macrophage metabolism. Cell Metabolism, 27(5), 1096–1110.e5. https://doi.org/10.1016/j.cmet.2018.03.014
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Luo, R., Yao, Y., Chen, Z., Wang, X., Liu, Q., Zhang, L., & Li, H. (2025). An examination of the LPS-TLR4 immune response through the analysis of molecular structures and protein–protein interactions. Cell Communication and Signaling, 23, 142. https://doi.org/10.1186/s12964-025-02149-4

Matsuzaka, T. (2020). Role of fatty acid elongase Elovl6 in the regulation of energy metabolism and pathophysiological significance in diabetes. Diabetology International, 12(1), 68–73. https://doi.org/10.1007/s13340-020-00481-3

Matsuzaka, T., Shimano, H., Yahagi, N., Kato, T., Atsumi, A., Yamamoto, T., Inoue, N., Ishikawa, M., Okada, S., Ishigaki, N., Iwasaki, H., Iwasaki, Y., Karasawa, T., Kumadaki, S., Matsui, T., Sekiya, M., Ohashi, K., Hasty, A. H., Nakagawa, Y., Takahashi, A., Suzuki, H., Yatoh, S., Sone, H., Toyoshima, H., Osuga, J., & Yamada, N. (2007). Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nature Medicine, 13(10), 1193–1202. https://doi.org/10.1038/nm1662

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Yoshida, K., Morishima, Y., Ano, S., Sakurai, H., Kishi, K., Mizutani, T., Shibata, T., Kobayashi, T., Abe, S., Suto, H., Suzuki, H., Matsuzaka, T., ... Hizawa, N. (2023). ELOVL6 deficiency aggravates allergic airway inflammation through the ceramide-S1P pathway in mice. Journal of Allergy and Clinical Immunology, 151(4), 1067–1080.e9. https://doi.org/10.1016/j.jaci.2022.12.808

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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/104588-
dc.description.abstract第二型糖尿病 (type 2 diabetes, T2D) 以胰島素阻抗為主要特徵,其中脂肪組織發炎扮演關鍵角色。ELOVL6 為參與脂質代謝之脂肪酸延長酶,可透過調控脂肪酸組成影響代謝穩態。本研究利用 3T3-L1 細胞模型,探討 ELOVL6 抑制 (knockdown, KD) 是否依脂肪細胞分化階段不同而調控發炎相關基因表現。於脂多醣 (lipopolysaccharide, LPS) 刺激下,ELOVL6 KD 在早期脂肪細胞中降低 Tnf 與 Il6 表現,並增加 Ccl2 表現;然而在成熟脂肪細胞中,則觀察到 Tnf 與 Il6 表現有上升趨勢、Ccl2 表現有下降趨勢,且脂質累積未出現 ELOVL6 KD 依賴性之顯著改變,顯示 ELOVL6 對發炎反應的影響可能受到脂肪細胞分化階段所影響。此結果顯示 ELOVL6 對發炎反應的調控可能具有分化階段依賴性(differentiation-stage-dependent),而非單純地抑制或促進發炎反應。其機制可能與脂肪酸組成改變所導致之脂質重塑有關,進而影響膜相關訊號傳遞與壓力反應途徑。整體而言,本研究顯示,在總脂質累積量未明顯改變的情況下,ELOVL6 KD 仍可能影響發炎相關基因表現,提示脂質組成或脂質重塑可能參與脂肪細胞發炎反應的調控。然而,此機制仍需進一步透過脂質體學分析加以驗證。zh_TW
dc.description.abstractType 2 diabetes (T2D) is characterized by insulin resistance, in which adipose tissue inflammation plays a key role. ELOVL6, a fatty acid elongase, regulates lipid composition and has been implicated in metabolic homeostasis, although its role in inflammation remains unclear. This study used a 3T3-L1 adipocyte differentiation model to examine whether ELOVL6 knockdown (KD) differentially affects inflammation-associated gene expression at different stages of adipocyte differentiation. Following lipopolysaccharide (LPS) stimulation, ELOVL6 KD reduced Tnf and Il6 expression but increased Ccl2 expression in early-stage adipocytes. In contrast, in mature adipocytes, ELOVL6 KD showed a tendency toward increased Tnf and Il6 expression and reduced Ccl2 expression, while not significantly affecting lipid accumulation. These findings suggest that ELOVL6 knockdown may influence inflammatory gene expression in a differentiation-stage-dependent manner. Since lipid accumulation was not significantly altered, the observed changes in inflammatory gene expression may be related to lipid remodeling rather than total lipid quantity; however, this mechanism requires further validation by lipidomic analysis.en
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dc.description.tableofcontents致謝 i
摘要 ii
Abstract iii
Chapter 1 Introduction 1
1.1 Global Burden of Obesity and Chronic Inflammation 1
1.2 Lipid-Mediated Inflammatory Signaling in Adipocytes 2
1.2.1 TLR4-Mediated Inflammatory Signaling 2
1.2.2 Membrane Structure and Lipid Raft Regulation 4
1.2.3 In Vitro Modeling Using 3T3-L1 Cells 5
1.3 ELOVL6 in Metabolic Regulation and Insulin Resistance 6
1.3.1 The ELOVL Family and Fatty Acid Elongation 6
1.3.2 ELOVL6 and Inflammatory Signaling 8
1.4 Research Gap and Hypothesis 10
1.5 Lipid Remodeling and Membrane-Dependent Signaling 12
1.6 Research Objective and Approach 14
Chapter 2 Materials and Methods 16
2.1 Cell Culture and Adipocyte Differentiation 16
2.2 siRNA Transfection and LPS Treatment 17
2.3 RNA Extraction and Quantitative Real-Time PCR 19
2.4 Oil Red O Staining and Quantification 19
2.5 Statistical Analysis 20
Chapter 3 Results 21
3.1 Validation of Elovl6 Knockdown 21
3.2 Effects of ELOVL6 Knockdown on Inflammatory Gene Expression in Early-Stage Adipocytes 21
3.3 Effects of ELOVL6 Knockdown on Inflammatory Gene Expression in Mature Adipocytes 23
3.4 Effects of ELOVL6 Knockdown on Lipid Accumulation 24
Chapter 4 Discussion 27
4.1 Overview of Key Findings 27
4.2 Stage-Dependent Regulation of Inflammatory Responses 27
4.3 Mechanistic Insights: Lipid Remodeling and Signaling Pathways 29
4.4 Implications for Adipocyte Biology and Metabolic Inflammation 31
Chapter 5 Limitations and Future Perspectives 33
Chapter 6 Conclusion and Way Forward 35
6.1 Conclusion and Way Forward 35
6.2 Translational Potential of ELOVL6 in Metabolic Diseases 36
6.3 Regional Perspectives: Context-Specific Approaches in Japan, Taiwan, and France 36
6.4 Implications for Metabolic Health and Future Strategies 37
References 39
Appendix Table 43
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dc.language.isoen-
dc.subjectELOVL6-
dc.subject脂肪細胞分化-
dc.subject發炎訊號傳遞-
dc.subject3T3-L1 細胞-
dc.subject脂多醣-
dc.subject第二型糖尿病-
dc.subjectELOVL6-
dc.subjectadipocyte differentiation-
dc.subjectinflammatory signaling-
dc.subject3T3-L1 cells-
dc.subjectlipopolysaccharide-
dc.subjecttype 2 diabetes-
dc.titleELOVL6於3T3-L1脂肪細胞中對脂多醣誘導發炎反應之調控作用zh_TW
dc.titleELOVL6 Regulates LPS-Induced Inflammation in 3T3-L1 Adipocytesen
dc.typeThesis-
dc.date.schoolyear114-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee饒梓明;楊俊逸zh_TW
dc.contributor.oralexamcommitteeTzu-Ming Jao;Jun-Yi Yangen
dc.subject.keywordELOVL6; 脂肪細胞分化; 發炎訊號傳遞; 3T3-L1 細胞; 脂多醣; 第二型糖尿病zh_TW
dc.subject.keywordELOVL6; adipocyte differentiation; inflammatory signaling; 3T3-L1 cells; lipopolysaccharide; type 2 diabetesen
dc.relation.page43-
dc.identifier.doi10.6342/NTU202601976-
dc.rights.note未授權-
dc.date.accepted2026-07-15-
dc.contributor.author-college醫學院-
dc.contributor.author-dept國際三校農業生技與健康醫療碩士學位學程-
dc.date.embargo-liftN/A-
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