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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/101725完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林甫容 | zh_TW |
| dc.contributor.advisor | Fu-Jung Lin | en |
| dc.contributor.author | 鄭羽涵 | zh_TW |
| dc.contributor.author | Yu-Han Cheng | en |
| dc.date.accessioned | 2026-02-26T17:02:14Z | - |
| dc.date.available | 2026-02-27 | - |
| dc.date.copyright | 2026-02-26 | - |
| dc.date.issued | 2026 | - |
| dc.date.submitted | 2026-01-15 | - |
| dc.identifier.citation | 1. Orginaization, W.H. Obesity and overweight. [cited 2025 May 7]; Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
2. 潘文涵, 國民營養健康狀況變遷調查（106 -109 年）. 2022, 衛生福利部國民健康署: 台北市. 3. Organization, W.H. Waist Circumference and Waist-Hip Ratio Report of a WHO Expert Consultation. 2011 [cited 2008 December 8-11]; Available from: https://iris.who.int/bitstream/handle/10665/44583/9789241501491_eng.pdf. 4. Health Promotion Administration, M.o.H.a.W.T. 成人健康體位標準. 2025; Available from: https://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=542&pid=9737. 5. 衛生福利部, 兒童與青少年生長身體質量指數(BMI)建議值. 2018. 6. Kerr, J.A.e.a., Global, regional, and national prevalence of child and adolescent overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021. The Lancet, 2025. 405(10481): p. 785 – 812. 7. Bray, G.A., K.K. Kim, and J.P.H. Wilding, Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev, 2017. 18(7): p. 715–723. 8. Bendor, C.D., et al., Cardiovascular morbidity, diabetes and cancer risk among children and adolescents with severe obesity. Cardiovasc Diabetol, 2020. 19(1): p. 79. 9. Twig, G., et al., Adolescent Obesity and Early-Onset Type 2 Diabetes. Diabetes Care, 2020. 43(7): p. 1487–1495. 10. Organization, W.H. The top 10 causes of death. [cited 2024 August 7]; Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. 11. 衛生福利部, 112年國人死因統計結果. June 17 2024: 台北. 12. Collaborators, G.A.B., Global, regional, and national prevalence of child and adolescent overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021. The Lancet, 2025. 405(10481): p. 785 – 812. 13. Simmonds, M., et al., Predicting adult obesity from childhood obesity: a systematic review and meta-analysis. Obes Rev, 2016. 17(2): p. 95–107. 14. Ivonne Palacios-Marin, D.S., Josep C. Jiménez-Chillarón, Laura Herrero, Marijana Todorčević, Childhood obesity: Implications on adipose tissue dynamics and metabolic health. Obesity Reviews, 2023. 24(12): p. e13627. 15. Meln, I., et al., Dietary calories and lipids synergistically shape adipose tissue cellularity during postnatal growth. Mol Metab, 2019. 24: p. 139–148. 16. Spalding, K.L., et al., Dynamics of fat cell turnover in humans. Nature, 2008. 453(7196): p. 783–7. 17. Zhang, X., et al., Global Prevalence of Overweight and Obesity in Children and Adolescents: A Systematic Review and Meta-Analysis. JAMA Pediatr, 2024. 178(8): p. 800–813. 18. Mannino, A., K. Sarapis, and G. Moschonis, The Effect of Maternal Overweight and Obesity Pre-Pregnancy and During Childhood in the Development of Obesity in Children and Adolescents: A Systematic Literature Review. Nutrients, 2022. 14(23). 19. Czarnobay, S.A., et al., Predictors of excess body weight concurrently affecting mother-child pairs: a 6 year follow-up. J Public Health (Oxf), 2023. 45(1): p. e10–e21. 20. Zheng, M., et al., Understanding the pathways between prenatal and postnatal factors and overweight outcomes in early childhood: a pooled analysis of seven cohorts. Int J Obes (Lond), 2023. 47(7): p. 574–582. 21. Rodrigo, N., et al., Diet Modification before or during Pregnancy on Maternal and Foetal Outcomes in Rodent Models of Maternal Obesity. Nutrients, 2022. 14(10). 22. Alfaradhi, M.Z., et al., Maternal Obesity in Pregnancy Developmentally Programs Adipose Tissue Inflammation in Young, Lean Male Mice Offspring. Endocrinology, 2016. 157(11): p. 4246–4256. 23. Chang, E., et al., Programming effects of maternal and gestational obesity on offspring metabolism and metabolic inflammation. Sci Rep, 2019. 9(1): p. 16027. 24. Lecoutre, S., et al., The Impact of Maternal Obesity on Adipose Progenitor Cells. Biomedicines, 2023. 11(12). 25. Yang, Q.Y., et al., Maternal obesity induces epigenetic modifications to facilitate Zfp423 expression and enhance adipogenic differentiation in fetal mice. Diabetes, 2013. 62(11): p. 3727–35. 26. Zhang, Q., et al., A Maternal High-Fat Diet Induces DNA Methylation Changes That Contribute to Glucose Intolerance in Offspring. Front Endocrinol (Lausanne), 2019. 10: p. 871. 27. Hieronimus, B. and R. Ensenauer, Influence of maternal and paternal pre-conception overweight/obesity on offspring outcomes and strategies for prevention. Eur J Clin Nutr, 2021. 75(12): p. 1735–1744. 28. Donkin, I., et al., Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans. Cell Metab, 2016. 23(2): p. 369–78. 29. de Castro Barbosa, T., et al., High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring. Mol Metab, 2016. 5(3): p. 184–197. 30. Arnetz, L., N.R. Ekberg, and M. Alvarsson, Sex differences in type 2 diabetes: focus on disease course and outcomes. Diabetes Metab Syndr Obes, 2014. 7: p. 409–20. 31. Colangeli, L., et al., The Crosstalk between Gut Microbiota and White Adipose Tissue Mitochondria in Obesity. Nutrients, 2023. 15(7). 32. Longo, M., et al., Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications. Int J Mol Sci, 2019. 20(9). 33. Liu, X., et al., An update on brown adipose tissue and obesity intervention: Function, regulation and therapeutic implications. Front Endocrinol (Lausanne), 2022. 13: p. 1065263. 34. Ricquier, D., Uncoupling protein 1 of brown adipocytes, the only uncoupler: a historical perspective. Front Endocrinol (Lausanne), 2011. 2: p. 85. 35. Cheng, L., et al., Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus. Adipocyte, 2021. 10(1): p. 48–65. 36. Singh, R., et al., Human Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues. Cells, 2021. 10(11). 37. Wu, J., et al., Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell, 2012. 150(2): p. 366–76. 38. Pilkington, A.C., H.A. Paz, and U.D. Wankhade, Beige Adipose Tissue Identification and Marker Specificity-Overview. Front Endocrinol (Lausanne), 2021. 12: p. 599134. 39. Hoang, A.C., et al., Mitochondrial RNA stimulates beige adipocyte development in young mice. Nat Metab, 2022. 4(12): p. 1684–1696. 40. Zheng, Y., et al., Mitochondria-associated regulation in adipose tissues and potential reagents for obesity intervention. Front Endocrinol (Lausanne), 2023. 14: p. 1132342. 41. Boychenko, S., et al., White-to-Beige and Back: Adipocyte Conversion and Transcriptional Reprogramming. Pharmaceuticals (Basel), 2024. 17(6). 42. Wang, Q.A., et al., Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med, 2013. 19(10): p. 1338–44. 43. Holtrup, B., et al., Puberty is an important developmental period for the establishment of adipose tissue mass and metabolic homeostasis. Adipocyte, 2017. 6(3): p. 224–233. 44. Bruder, J. and T. Fromme, Global Adipose Tissue Remodeling During the First Month of Postnatal Life in Mice. Front Endocrinol (Lausanne), 2022. 13: p. 849877. 45. Rondini, E.A., et al., Single cell functional genomics reveals plasticity of subcutaneous white adipose tissue (WAT) during early postnatal development. Mol Metab, 2021. 53: p. 101307. 46. Trevor, L.V., et al., Adipose Tissue: A Source of Stem Cells with Potential for Regenerative Therapies for Wound Healing. J Clin Med, 2020. 9(7). 47. Ferrero, R., P. Rainer, and B. Deplancke, Toward a Consensus View of Mammalian Adipocyte Stem and Progenitor Cell Heterogeneity. Trends Cell Biol, 2020. 30(12): p. 937–950. 48. Hepler, C., L. Vishvanath, and R.K. Gupta, Sorting out adipocyte precursors and their role in physiology and disease. Genes Dev, 2017. 31(2): p. 127–140. 49. Maniyadath, B., et al., Adipose tissue at single-cell resolution. Cell Metab, 2023. 35(3): p. 386–413. 50. Schwalie, P.C., et al., A stromal cell population that inhibits adipogenesis in mammalian fat depots. Nature, 2018. 559(7712): p. 103–108. 51. Merrick, D., et al., Identification of a mesenchymal progenitor cell hierarchy in adipose tissue. Science, 2019. 364(6438). 52. Tang, F., et al., mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods, 2009. 6(5): p. 377–82. 53. Zheng, G.X., et al., Massively parallel digital transcriptional profiling of single cells. Nat Commun, 2017. 8: p. 14049. 54. Shao, X., et al., scCATCH: Automatic Annotation on Cell Types of Clusters from Single-Cell RNA Sequencing Data. iScience, 2020. 23(3): p. 100882. 55. Jiang, C.L., et al., Early-life ketone body signalling promotes beige fat biogenesis through changes in histone acetylome and β-hydroxybutyrylome. Nat Metab, 2025. 56. de Moura, E.D.M., et al., Diet-induced obesity in animal models: points to consider and influence on metabolic markers. Diabetol Metab Syndr, 2021. 13(1): p. 32. 57. Lang, P., et al., Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL/6 mice. Sci Rep, 2019. 9(1): p. 19556. 58. Nagy, C. and E. Einwallner, Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT). J Vis Exp, 2018(131). 59. Kozak, L.P., et al., The early nutritional environment of mice determines the capacity for adipose tissue expansion by modulating genes of caveolae structure. PLoS One, 2010. 5(6): p. e11015. 60. Miller, C.N., et al., Isoproterenol Increases Uncoupling, Glycolysis, and Markers of Beiging in Mature 3T3-L1 Adipocytes. PLoS One, 2015. 10(9): p. e0138344. 61. T, L.R., et al., MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry. Cell Commun Signal, 2016. 14: p. 2. 62. Lopez-Mejia, I.C., et al., Role of cell cycle regulators in adipose tissue and whole body energy homeostasis. Cell Mol Life Sci, 2018. 75(6): p. 975–987. 63. Zatterale, F., et al., Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Front Physiol, 2019. 10: p. 1607. 64. Chen, N. and J. Wang, Wnt/β-Catenin Signaling and Obesity. Front Physiol, 2018. 9: p. 792. 65. Sevillano, J., et al., Pleiotrophin deletion alters glucose homeostasis, energy metabolism and brown fat thermogenic function in mice. Diabetologia, 2019. 62(1): p. 123–135. 66. Wong, J.C., et al., A glucocorticoid- and diet-responsive pathway toggles adipocyte precursor cell activity in vivo. Sci Signal, 2016. 9(451): p. ra103. 67. Wrann, C.D., et al., FOSL2 promotes leptin gene expression in human and mouse adipocytes. J Clin Invest, 2012. 122(3): p. 1010–21. 68. Zhang, X., et al., FOXO3a regulates lipid accumulation and adipocyte inflammation in adipocytes through autophagy : Role of FOXO3a in obesity. Inflamm Res, 2021. 70(5): p. 591–603. 69. Ding, F., et al., Adipocyte-secreted PRELP promotes adipocyte differentiation and adipose tissue fibrosis by binding with p75(NTR) to activate FAK/MAPK signaling. Int J Biol Macromol, 2024. 279(Pt 4): p. 135376. 70. Lei, X., et al., Thromboxane synthase deficiency improves insulin action and attenuates adipose tissue fibrosis. Am J Physiol Endocrinol Metab, 2015. 308(9): p. E792–804. 71. Feng, T., et al., Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2. Nat Commun, 2022. 13(1): p. 5208. 72. Cox, A.R., et al., STAT1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity in Obesity. Diabetes, 2020. 69(12): p. 2630–2641. 73. Nodari, A., et al., Interferon regulatory factor 7 impairs cellular metabolism in aging adipose-derived stromal cells. J Cell Sci, 2021. 134(11). 74. Nahmgoong, H., et al., Distinct properties of adipose stem cell subpopulations determine fat depot-specific characteristics. Cell Metab, 2022. 34(3): p. 458–472.e6. 75. Heslehurst, N., et al., The association between maternal body mass index and child obesity: A systematic review and meta-analysis. PLoS Med, 2019. 16(6): p. e1002817. 76. Haberman, M., et al., Paternal high-fat diet affects weight and DNA methylation of their offspring. Sci Rep, 2024. 14(1): p. 19874. 77. Ashino, N.G., et al., Maternal high-fat feeding through pregnancy and lactation predisposes mouse offspring to molecular insulin resistance and fatty liver. J Nutr Biochem, 2012. 23(4): p. 341–8. 78. Bringhenti, I., et al., Maternal obesity during the preconception and early life periods alters pancreatic development in early and adult life in male mouse offspring. PLoS One, 2013. 8(1): p. e55711. 79. Samuelsson, A.M., et al., Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension, 2008. 51(2): p. 383–92. 80. Wei, Y., et al., Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Natl Acad Sci U S A, 2014. 111(5): p. 1873–8. 81. Binder, N.K., N.J. Hannan, and D.K. Gardner, Paternal diet-induced obesity retards early mouse embryo development, mitochondrial activity and pregnancy health. PLoS One, 2012. 7(12): p. e52304. 82. Fullston, T., et al., Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an "obesogenic" diet. Physiol Rep, 2015. 3(3). 83. Wang, C.Y. and J.K. Liao, A mouse model of diet-induced obesity and insulin resistance. Methods Mol Biol, 2012. 821: p. 421–33. 84. Laboratory, T.J. Phenotype Information for B6 DIO. JAX® Mice Strains C57BL/6J DIO and C57BL/6J DIO Control n.d.; Available from: https://www.jax.org/jax-mice-and-services/strain-data-sheet-pages/phenotype-information-380050. 85. Research Diets, I. Diet-Induced Obesity (DIO). Available from: https://researchdiets.com/opensource-diets/in-stock-diets#dio-series-diets. 86. Jiang, T., et al., Diet-induced obesity in C57BL/6J mice causes increased renal lipid accumulation and glomerulosclerosis via a sterol regulatory element-binding protein-1c-dependent pathway. J Biol Chem, 2005. 280(37): p. 32317–25. 87. Savetsky, I.L., et al., Lymphatic Function Regulates Contact Hypersensitivity Dermatitis in Obesity. J Invest Dermatol, 2015. 135(11): p. 2742–2752. 88. Burcelin, R., et al., Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet. Am J Physiol Endocrinol Metab, 2002. 282(4): p. E834–42. 89. Zhang, T., et al., Ashitaba (Angelica keiskei) extract prevents adiposity in high-fat diet-fed C57BL/6 mice. Food Funct, 2015. 6(1): p. 135–45. 90. Iñiguez, M., et al., Agaricus bisporus supplementation reduces high-fat diet-induced body weight gain and fatty liver development. J Physiol Biochem, 2018. 74(4): p. 635–646. 91. Chusyd, D.E., et al., Relationships between Rodent White Adipose Fat Pads and Human White Adipose Fat Depots. Front Nutr, 2016. 3: p. 10. 92. Börgeson, E., J. Boucher, and C.E. Hagberg, Of mice and men: Pinpointing species differences in adipose tissue biology. Front Cell Dev Biol, 2022. 10: p. 1003118. 93. van Beek, L., et al., The limited storage capacity of gonadal adipose tissue directs the development of metabolic disorders in male C57Bl/6J mice. Diabetologia, 2015. 58(7): p. 1601–9. 94. Li, D., et al., Gonadal white adipose tissue-derived exosomal MiR-222 promotes obesity-associated insulin resistance. Aging (Albany NY), 2020. 12(22): p. 22719–22743. 95. Lee, Y.H., et al., In vivo identification of bipotential adipocyte progenitors recruited by β3-adrenoceptor activation and high-fat feeding. Cell Metab, 2012. 15(4): p. 480–91. 96. Palacios-Marin, I., et al., Childhood obesity: Implications on adipose tissue dynamics and metabolic health. Obes Rev, 2023. 24(12): p. e13627. 97. Vishvanath, L., et al., Pdgfrβ+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice. Cell Metab, 2016. 23(2): p. 350–9. 98. Hepler, C., et al., Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice. Elife, 2017. 6. 99. Bilal, M., et al., Fate of adipocyte progenitors during adipogenesis in mice fed a high-fat diet. Mol Metab, 2021. 54: p. 101328. 100. Hishida, T., et al., The role of C/EBPdelta in the early stages of adipogenesis. Biochimie, 2009. 91(5): p. 654–7. 101. Balamurugan, K. and E. Sterneck, The many faces of C/EBPδ and their relevance for inflammation and cancer. Int J Biol Sci, 2013. 9(9): p. 917–33. 102. Melillo, R.M., et al., Critical role of the HMGI(Y) proteins in adipocytic cell growth and differentiation. Mol Cell Biol, 2001. 21(7): p. 2485–95. 103. Arce-Cerezo, A., et al., HMGA1 overexpression in adipose tissue impairs adipogenesis and prevents diet-induced obesity and insulin resistance. Sci Rep, 2015. 5: p. 14487. 104. Waki, H., et al., Global mapping of cell type-specific open chromatin by FAIRE-seq reveals the regulatory role of the NFI family in adipocyte differentiation. PLoS Genet, 2011. 7(10): p. e1002311. 105. Eguchi, J., et al., Interferon regulatory factors are transcriptional regulators of adipogenesis. Cell Metab, 2008. 7(1): p. 86–94. 106. Dutta, A.B., et al., Kinetic networks identify TWIST2 as a key regulatory node in adipogenesis. Genome Res, 2023. 33(3): p. 314–331. 107. Mansoori, B., et al., HMGA2 as a Critical Regulator in Cancer Development. Genes (Basel), 2021. 12(2). 108. Rogalla, P., et al., HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors. Am J Pathol, 1996. 149(3): p. 775–9. 109. Xi, Y., et al., HMGA2 promotes adipogenesis by activating C/EBPβ-mediated expression of PPARγ. Biochem Biophys Res Commun, 2016. 472(4): p. 617–23. 110. Vergnes, L., et al., SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression. J Lipid Res, 2016. 57(3): p. 410–21. 111. Inoue, J., et al., Proteolytic activation of SREBPs during adipocyte differentiation. Biochem Biophys Res Commun, 2001. 283(5): p. 1157–61. 112. Bauer, S., et al., Sterol regulatory element-binding protein 2 (SREBP2) activation after excess triglyceride storage induces chemerin in hypertrophic adipocytes. Endocrinology, 2011. 152(1): p. 26–35. 113. Salma, N., et al., Tfe3 and Tfeb Transcriptionally Regulate Peroxisome Proliferator-Activated Receptor γ2 Expression in Adipocytes and Mediate Adiponectin and Glucose Levels in Mice. Mol Cell Biol, 2017. 37(15). 114. Fujimoto, Y., et al., TFE3 controls lipid metabolism in adipose tissue of male mice by suppressing lipolysis and thermogenesis. Endocrinology, 2013. 154(10): p. 3577–88. 115. Chen, L., et al., ZFP57 suppress proliferation of breast cancer cells through down-regulation of MEST-mediated Wnt/β-catenin signalling pathway. Cell Death Dis, 2019. 10(3): p. 169. 116. Shamis, Y., et al., Maternal and zygotic Zfp57 modulate NOTCH signaling in cardiac development. Proc Natl Acad Sci U S A, 2015. 112(16): p. E2020–9. 117. Fahim, S.A., et al., MEIS1: From functional versatility to post-transcriptional/translational regulation. Life Sci, 2025. 374: p. 123683. 118. Gulyaeva, O., et al., Sox9-Meis1 Inactivation Is Required for Adipogenesis, Advancing Pref-1(+) to PDGFRα(+) Cells. Cell Rep, 2018. 25(4): p. 1002–1017.e4. 119. Theka, I., et al., Reduced expression of Paternally Expressed Gene-3 enhances somatic cell reprogramming through mitochondrial activity perturbation. Sci Rep, 2017. 7(1): p. 9705. 120. Ghimire, S. and J. Kim, PEG3 controls lipogenesis through ACLY. PLoS One, 2021. 16(5): p. e0252354. 121. Curley, J.P., et al., Increased body fat in mice with a targeted mutation of the paternally expressed imprinted gene Peg3. Faseb j, 2005. 19(10): p. 1302–4. 122. Galán-Martínez, J., et al., TCFL5 deficiency impairs the pachytene to diplotene transition during spermatogenesis in the mouse. Sci Rep, 2022. 12(1): p. 10956. 123. Shi, Y., et al., The mouse transcription factor-like 5 gene encodes a protein localized in the manchette and centriole of the elongating spermatid. Andrology, 2013. 1(3): p. 431–9. 124. Stumm, J., et al., Odd skipped-related 1 (Osr1) identifies muscle-interstitial fibro-adipogenic progenitors (FAPs) activated by acute injury. Stem Cell Res, 2018. 32: p. 8–16. 125. Smith, M.R., L.R.F. Satter, and A. Vargas-Hernández, STAT5b: A master regulator of key biological pathways. Front Immunol, 2022. 13: p. 1025373. 126. Richard, A.J., et al., Loss of Adipocyte STAT5 Confers Increased Depot-Specific Adiposity in Male and Female Mice That Is Not Associated With Altered Adipose Tissue Lipolysis. Front Endocrinol (Lausanne), 2022. 13: p. 812802. 127. Selleri, L., et al., The TALE homeodomain protein Pbx2 is not essential for development and long-term survival. Mol Cell Biol, 2004. 24(12): p. 5324–31. 128. Lin, J., et al., Coexpression of HOXA6 and PBX2 promotes metastasis in gastric cancer. Aging (Albany NY), 2021. 13(5): p. 6606–6624. 129. Weng, X., et al., The role of Bach2 in regulating CD8 + T cell development and function. Cell Commun Signal, 2024. 22(1): p. 169. 130. Contreras, A., et al., BACH2 in TRegs Limits the Number of Adipose Tissue Regulatory T Cells and Restrains Type 2 Immunity to Fungal Allergens. J Immunol Res, 2022. 2022: p. 6789055. 131. Cao, G., et al., The rules and regulatory mechanisms of FOXO3 on inflammation, metabolism, cell death and aging in hosts. Life Sci, 2023. 328: p. 121877. 132. Morris, B.J., et al., FOXO3: A Major Gene for Human Longevity--A Mini-Review. Gerontology, 2015. 61(6): p. 515–25. 133. Zhao, Y. and Y.S. Liu, Longevity Factor FOXO3: A Key Regulator in Aging-Related Vascular Diseases. Front Cardiovasc Med, 2021. 8: p. 778674. 134. Feng, P., et al., Enhancer-mediated FOXO3 expression promotes MSC adipogenic differentiation by activating autophagy. Biochim Biophys Acta Mol Basis Dis, 2024. 1870(2): p. 166975. 135. Tolomeo, M., A. Cavalli, and A. Cascio, STAT1 and Its Crucial Role in the Control of Viral Infections. Int J Mol Sci, 2022. 23(8). 136. Lee, C.J., et al., Stat2 stability regulation: an intersection between immunity and carcinogenesis. Exp Mol Med, 2020. 52(9): p. 1526–1536. 137. Kuroda, M., et al., Interferon regulatory factor 7 mediates obesity-associated MCP-1 transcription. PLoS One, 2020. 15(5): p. e0233390. 138. Wang, G., et al., Distinct adipose progenitor cells emerging with age drive active adipogenesis. Science, 2025. 388(6745): p. eadj0430. 139. Harlan, B., et al., Single-cell chromatin accessibility and lipid profiling reveals SCD1-dependent metabolic shift in adipocytes induced by bariatric surgery. PLoS One, 2021. 16(12): p. e0261783. 140. Oben, J.A., et al., Maternal obesity during pregnancy and lactation programs the development of offspring non-alcoholic fatty liver disease in mice. J Hepatol, 2010. 52(6): p. 913–20. 141. Aizawa, S., A. Tochihara, and Y. Yamamuro, Paternal high-fat diet alters triglyceride metabolism-related gene expression in liver and white adipose tissue of male mouse offspring. Biochem Biophys Rep, 2022. 31: p. 101330. 142. Savva, C., et al., Maternal high-fat diet programs white and brown adipose tissue lipidome and transcriptome in offspring in a sex- and tissue-dependent manner in mice. Int J Obes (Lond), 2022. 46(4): p. 831–842. 143. Hayakawa, T., et al., Reorganization of the DNA replication landscape during adipogenesis is closely linked with adipogenic gene expression. J Cell Sci, 2023. 136(2). 144. Fan, H., et al., Cold-Inducible Klf9 Regulates Thermogenesis of Brown and Beige Fat. Diabetes, 2020. 69(12): p. 2603–2618. 145. Gupta, R.K., et al., Transcriptional control of preadipocyte determination by Zfp423. Nature, 2010. 464(7288): p. 619–23. 146. Gupta, R.K., et al., Zfp423 expression identifies committed preadipocytes and localizes to adipose endothelial and perivascular cells. Cell Metab, 2012. 15(2): p. 230–9. 147. Lee, J.E., et al., Transcriptional and Epigenomic Regulation of Adipogenesis. Mol Cell Biol, 2019. 39(11). 148. Fu, M., et al., Cyclin D1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment. J Biol Chem, 2005. 280(17): p. 16934–41. 149. Fox, K.E., et al., Regulation of cyclin D1 and Wnt10b gene expression by cAMP-responsive element-binding protein during early adipogenesis involves differential promoter methylation. J Biol Chem, 2008. 283(50): p. 35096–105. 150. Marquez, M.P., et al., The Role of Cellular Proliferation in Adipogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells. Stem Cells Dev, 2017. 26(21): p. 1578–1595. 151. Wu, R., et al., Genetically prolonged beige fat in male mice confers long-lasting metabolic health. Nat Commun, 2023. 14(1): p. 2731. 152. Liu, L., et al., Osr1 Regulates Macrophage-mediated Liver Inflammation in Nonalcoholic Fatty Liver Disease Progression. Cell Mol Gastroenterol Hepatol, 2023. 15(5): p. 1117–1133. 153. Zhang, Y., et al., OSR1 is a novel epigenetic silenced tumor suppressor regulating invasion and proliferation in renal cell carcinoma. Oncotarget, 2017. 8(18): p. 30008–30018. 154. Zong, L. and Y. Sun, OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling. Autoimmunity, 2021. 54(8): p. 561–568. 155. Chou, Y.T., et al., CITED2 functions as a molecular switch of cytokine-induced proliferation and quiescence. Cell Death Differ, 2012. 19(12): p. 2015–28. 156. Wu, Q., et al., Cited2 regulates proliferation and survival in young and old mouse cardiac stem cells. BMC Mol Cell Biol, 2019. 20(1): p. 25. 157. Kuna, M. and M.J. Soares, Cited2 is a key regulator of placental development and plasticity. Bioessays, 2024. 46(8): p. e2300118. 158. Mathsyaraja, H. and M.C. Ostrowski, Setting Snail2's pace during EMT. Nat Cell Biol, 2012. 14(11): p. 1122–3. 159. Pérez-Mancera, P.A., et al., Adipose tissue mass is modulated by SLUG (SNAI2). Hum Mol Genet, 2007. 16(23): p. 2972–86. 160. Pei, H., et al., Krüppel-like factor KLF9 regulates PPARγ transactivation at the middle stage of adipogenesis. Cell Death Differ, 2011. 18(2): p. 315–27. 161. Li, D., et al., Krüppel-like factor-6 promotes preadipocyte differentiation through histone deacetylase 3-dependent repression of DLK1. J Biol Chem, 2005. 280(29): p. 26941–52. 162. Shao, M., et al., Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program. Cell Metab, 2016. 23(6): p. 1167–1184. 163. Shao, M., et al., Fetal development of subcutaneous white adipose tissue is dependent on Zfp423. Mol Metab, 2017. 6(1): p. 111–124. 164. Indrio, F., et al., Epigenetic Matters: The Link between Early Nutrition, Microbiome, and Long-term Health Development. Front Pediatr, 2017. 5: p. 178. 165. Cai, S., et al., Nutritional Status Impacts Epigenetic Regulation in Early Embryo Development: A Scoping Review. Adv Nutr, 2021. 12(5): p. 1877–1892. 166. Bernhardt, L., et al., A genome-wide transcriptomic analysis of embryos fathered by obese males in a murine model of diet-induced obesity. Sci Rep, 2021. 11(1): p. 1979. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/101725 | - |
| dc.description.abstract | 肥胖主要源於脂肪組織的過度積累，尤其是白色脂肪組織（white adipose tissue, WAT）的擴張。研究指出，兒童及青少年階段的脂肪重塑機制決定成年後的脂肪細胞數量，而親代代謝狀態也可能對子代出生後的代謝產生長期影響。然而，親代肥胖是否在子代出生早期就已改變脂肪前驅細胞的組成、轉錄調控以及分化潛力仍不清楚。本研究以C57BL/6J小鼠為模型，以一般飲食組（Chow Diet, ChowD）與高脂飲食組（HFD）建立母體肥胖子代（MO-F1）、父母雙方肥胖子代（PO-F1）與代謝正常子代（Ln-F1）三組。結果顯示，MO-F1與PO-F1出生第九天的體重與iWAT重量顯著上升，並伴隨棕色脂肪組織與肝臟內脂質堆積的現象。體外iWAT基質血管細胞（stromal vascular fraction, SVF）分化後，MO-F1與PO-F1的產熱基因表現顯著下降，其中MO-F1同時表現出較高的脂肪分化能力。進一步以單細胞RNA定序（scRNA-seq）分析，iWAT SVF中包含三群主要脂肪前驅細胞的細胞群（ASC1a、ASC1b、ASC1c）。其中，ASC1a在MO-F1中比例最高且偏向脂肪生成、ASC1b在PO-F1中富集且呈現促發炎與代謝失衡特徵，而ASC1c則在Ln-F1組中比例最高，但在三組子代皆呈現具有維持細胞穩定與抗肥胖潛力，顯示不同的親代肥胖在出生早期就已改變子代脂肪前驅細胞細胞群的組成與功能。此外，子代脂肪細胞不僅受到脂肪前驅細胞群的影響，也可能受到上游轉錄因子的調控。結合先前實驗室bulk-RNA sequence的結果與不同類型的脂肪細胞模型，初步結果顯示在不同組別間（Ln-F1, MO-F1, PO-F1）候選轉錄因子早在胚胎期的表現量就已存在趨勢性的差異，但在出生後第九天的表現量在組間則無顯差。進一步透過loss-of-function實驗初步探討候選轉錄因子的在脂肪分化中的潛在調控角色，未來可結合gain-of-function以及不同親代肥胖的SVF，直接比較不同親代肥胖下，子代脂肪前驅細胞在基因調控與分化功能上的差異。綜合上述，本研究證實親代肥胖自胚胎期可能就已影響子代脂肪前驅細胞的轉錄調控，且同時改變出生後脂肪組織的細胞組成與代謝功能，顯示親代代謝狀態可跨代影響子代脂肪前驅細胞的調控，為日後暸解肥胖的跨代代謝潛在機制提供研究方向。 | zh_TW |
| dc.description.abstract | Obesity primarily results from excessive expansion of adipose tissue, particularly the enlargement of white adipose tissue (WAT). Previous studies indicate that adipose tissue remodeling during childhood and adolescence largely determines adult adipocyte numbers, and that parental metabolic status can exert long-lasting effects on offspring metabolism. However, whether parental obesity alters adipose progenitor composition, transcriptional regulation, and differentiation potential during early postnatal development remains unclear.
In this study, we established three groups of C57BL/6J offspring—metabolically normal controls (Ln-F1), maternal-obesity offspring (MO-F1), and parental-obesity offspring (PO-F1) - by providing parents either a chow diet (ChowD) or a high-fat diet (HFD). At postnatal day 9 (P9), both MO-F1 and PO-F1 displayed higher body weight and heavier iWAT mass compared with Ln-F1, along with greater lipid accumulation in brown adipose tissue (BAT) and the liver. Upon in vitro differentiation of iWAT stromal vascular fraction (SVF) cells, MO-F1 and PO-F1 showed lower expression of thermogenic genes, whereas MO-F1 additionally exhibited higher adipogenic capacity. Single-cell RNA sequencing (scRNA-seq) identified three major adipose progenitor clusters within iWAT SVF—ASC1a, ASC1b, and ASC1c. ASC1a was more abundant in MO-F1 and displayed a transcriptional profile associated with adipogenesis; ASC1b was enriched in PO-F1 and showed signatures related to inflammation and metabolic imbalance; ASC1c was more prevalent in Ln-F1 and exhibited features linked to cellular homeostasis and potential anti-obesity properties. These findings indicate that parental obesity modifies offspring adipose progenitor composition and functional states as early as the neonatal stage. Because progenitor identity is further shaped by upstream transcriptional regulators, we integrated previous bulk RNA-seq data from our laboratory with multiple adipocyte differentiation models to examine candidate regulators. Preliminary analyses revealed group-specific trends in the expression of several transcriptional regulators during embryonic development, although such differences were not evident at P9. Loss-of-function experiments provided initial evidence supporting the regulatory roles of these candidates in adipocyte differentiation. Future studies involving gain-of-function approaches and SVF derived from different parental obesity groups will help clarify how parental metabolic status influences transcriptional regulation and differentiation potential in offspring adipose progenitors. Taken together, our findings suggest that parental obesity may shape the transcriptional programming of adipose progenitors as early as embryogenesis and subsequently alter postnatal adipose tissue cellular composition and metabolic function. These results provide insight into how parental metabolic status may exert intergenerational effects on offspring adipose development and obesity susceptibility. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2026-02-26T17:02:14Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2026-02-26T17:02:14Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 謝辭 i
摘要 ii Abstract iv 目次 vi 圖次 xiii 表次 xv 縮寫表 xvi 第一章 緒論 1 第一節 前言 1 第二節 文獻回顧 2 ㄧ、肥胖流行的現況及趨勢 2 1. 肥胖定義 2 2. 肥胖的現況與趨勢 2 二、肥胖相關慢性疾病與十大死因 3 三、親代肥胖與子代肥胖的關聯 3 1. 母親肥胖（Maternal Obesity） 4 2. 父親肥胖（Parternal Obesity） 4 四、脂肪細胞的種類與功能之介紹 5 1. 白色脂肪細胞（white adipocytes） 5 2. 棕色脂肪細胞（brown adipocytes） 6 3. 米色脂肪細胞（beige adipocytes） 7 五、脂肪的發育時間 7 六、根據scRNA-seq定義iWAT中的脂肪前驅細胞 8 1. Adipose stem‑like cells (ASLC) 8 2. Preadipocytes (PreAD) 9 3. Adipogenesis-regulatory cell (Aregs) 9 七、脂肪組織單細胞定序 12 八、single-cell Cluster-based automatic Annotation Toolkit for Cellular Heterogeneity（scCATCH） 14 第二章 探討親代肥胖對子代脂肪前驅細胞異質性與分化潛力的影響 16 第一節 前言與實驗設計 16 ㄧ、前言 16 二、實驗設計 17 第二節 材料與方法 18 ㄧ、小鼠飼養 18 1. 小鼠品系與飼養條件: 18 2. 飼料配製 18 二、葡萄糖耐受性測試（Oral Glucose Tolerance Test, OGTT） 20 三、小鼠犧牲 20 四、細胞培養與分化 20 1. 細胞培養、繼代以及數細胞 20 2. 凍細胞與解細胞 21 3. 培養基配置 21 4. 細胞分化 21 五、油紅染色 (Oil Red O staining, ORO staining) 24 六、小鼠組織切片與染色 24 1. 組織切片 24 2. 量化脂肪細胞大小 24 3. 組織切片免疫螢光染色 25 4. 定量UCP1免疫螢光強度量化 25 七、RNA抽取與反轉錄成cDNA 26 1. 抽取RNA 26 2. 去除DNA 26 3. 反轉錄成cDNA 27 4.Quantitive Real-time PCR（qPCR） 27 八、單細胞RNA定序 27 1. 收取小鼠SVF 27 2. SVFs細胞培養 28 3. 定序與細胞library建置 28 4. 篩選與標準化（Normalization） 29 5. 數據降維（dimensional reduction）與細胞分群（cell clustering） 29 6. 定義細胞群 30 7. 作圖 30 8. 細胞時序性軌跡分析（pseudotimporal trajectory analysis） 30 9. Gene Ontology (GO) 30 九、scCATCH 31 十、統計方法 31 第三節 實驗結果 32 一、高油脂飲食誘導親代肥胖促進體重與葡萄糖不耐受性增加 32 二、親代肥胖顯著促進子代體重上升並伴隨皮下白色脂肪組織的累積 32 三、親代肥胖趨勢性使子代早期脂肪細胞肥大與組織異位脂質沉積 33 四、雙親肥胖相較於母親肥胖更顯著降低子代SVF分化脂肪細胞的產熱基因表現 34 五、母親肥胖相較於父母雙方肥胖子代的SVF白色脂肪的分化效率更顯著 35 六、定義iWAT SVFs單細胞定序10群細胞群 35 七、ASC1a、ASC1b、ASC1c為子代iWAT SVFs脂肪前驅細胞分化早期細胞群 37 八、scCATCH驗證iWAT SVF細胞群定義的準確性 37 九、親代肥胖顯著改變子代iWAT SVF脂肪前驅細胞的細胞群比例 38 十、親代雙方肥胖顯著改變子代ASC1b脂肪前驅細胞基因表現及代謝相關途徑 38 十一、ASC1b群上調差異表現基因發現潛在脂肪分化相關的基因 39 十二、母親肥胖顯著改變子代ASC1a脂肪前驅細胞基因表現及代謝相關途徑 40 十三、ASC1a群上調差異表現基因發現潛在脂肪分化相關的候選基因 40 十四、代謝正常的Ln-F1小鼠在ASC1c脂肪前驅細胞基因表現及代謝相關途徑 43 十五、ASC1c下調差異表現基因顯示潛在抗肥胖相關的候選基因 43 十六、ASC1脂肪前驅細胞的再分群顯示五個功能性微細胞群 44 第四節 討論 79 ㄧ、親代肥胖動物模型 79 1. 母親肥胖 79 2. 父親肥胖 79 二、小鼠肥胖的定義 81 三、肥胖中的白色脂肪組織 83 四、肥胖中的脂肪前驅細胞 84 五、MO-F1組前驅細胞出現與成年類似的免疫狀態，顯示早期活化而非成年狀態 85 六、MO-F1在ASC1a的潛在轉錄因子 87 1. C/ebpδ (CCAAT/enhancer-binding protein delta) 87 2. Hmga1 (High Mobility Group AT-Hook 1) 87 3. Nfib (Nuclear Factor I B): 87 4. Irf9 (Interferon Regulatory Factor 9) 87 5. Twist2 (Twist Family BHLH Transcription Factor 2) 87 6. Hmga2 (High mobility group protein AT-hook 2) 88 7. Srebf2（Sterol regulatory element-binding protein 2） 88 8. Nfyc（Nuclear transcription factor Y subunit gamma） 88 9. Tfe3 （Transcription Factor Binding To IGHM Enhancer 3） 88 10. Zfp57（Zinc finger protein 57） 88 11. Meis1（Meis homeobox 1） 89 12. Peg3（Paternally-expressed gene 3） 89 13. Tcfl5（Transcription Factor Like 5） 89 14. Osr1（Odd-Skipped Related Transcription Factor 1） 89 15. Stat5b （Signal Transducer And Activator Of Transcription 5B） 89 16. Sp2（Sp2 Transcription Factor） 90 17. Pbx2（PBX Homeobox 2） 90 18. Bach2（BTB Domain And CNC Homolog 2） 90 七、PO-F1在ASC1b的潛在轉錄因子 91 1. Zscan26（Zinc Finger and SCAN domain containing 26） 91 2. Foxo3（Forkhead box O-3） 91 3. Fosl2（FOS Like 2, AP-1 Transcription Factor Subunit） 91 八、Ln-F1在ASC1c的潛在轉錄因子 92 1. Stat1（Signal Transducer and Activator of Transcription 1） 92 2. Stat2（Signal Transducer and Activator of Transcription 2） 92 3. Irf7（Interferon Regulatory Factor 7） 92 4. Sp100（SP100 Nuclear Antigen） 92 九、未來展望： 93 1. ASC1a, ASC1b, ASC1c脂肪前驅細胞在親代肥胖下是否呈現差異性的調控 93 2. 表觀遺傳藉由親代肥胖調控子代脂肪前驅細胞功能中的潛在方向 94 3. 探討子代iWAT脂肪前驅細胞中轉錄基因米色化的潛力 95 第五節 結論 96 第三章 初探候選轉錄因子在脂肪分化與產熱功能調控中的潛在角色 97 第一節 前言與實驗設計 97 ㄧ、前言 97 二、實驗設計 98 1. 3T3-L1: 98 2. Mouse embryonic fibroblasts（MEF）與Stromal vascular fraction（SVF） 98 3. 3T3-L1 + Plasmid 過表現（overexpression, OE） 98 4. 3T3-L1 + shRNA 基因敲落（knockdown, KD） 98 第二節 材料與方法 99 ㄧ、小鼠犧牲 99 二、細胞培養與分化 99 1. 細胞培養 99 2. 脂肪細胞分化 99 3. 細胞存活率 99 三、建構載體（Construction of plasmids） 100 1. 設計primer 100 2. DNA進行聚合反應 100 3. A tailing 102 4. 接合反應（Ligation） 102 5. 轉型作用（Transformation） 102 6. Colony PCR 103 7. 純化質體DNA 104 8. 質體DNA鑑定 104 9. 定序 104 10. Insert與vector的製備 105 11. DNA Ligation 105 12. 重組質體轉型 （Transformation） 106 13. 重組質體鑑定 106 14. 轉染（Transfection） 107 四、shRNA 107 1. 核糖核酸干擾（shRNA knockdown） 107 2. 慢病毒感染（Lentivirus infection） 109 五、統計方法 109 第三節 實驗結果 110 ㄧ、候選轉錄因子在3T3-L1脂肪細胞分化過程中的表現趨勢 110 二、候選基因在親代肥胖的子代E13.5 MEF中的表現量趨勢下降 110 三、不同親代組別子代脂肪前驅細胞的候選基因間表現並無顯著差異 111 四、脂肪前驅細胞中候選基因的單細胞定序分析顯示子代組別間差異不明顯 111 五、候選基因loss-of-function模型建立對3T3-L1脂肪分化與Ucp1表現的影響 111 六、候選基因過表現質體的建立及其應用潛力 112 第四節 討論 120 ㄧ、候選轉錄因子的一般功能及其在脂肪細胞中的潛在作用 120 1. Ccnd1（Cyclin D1）： 120 2. Osr1（Odd-Skipped Related Transcription Factor 1）： 120 3. Cited2（Cbp/p300-interacting transactivator 2 with Glu/Asp-rich carboxy-terminal domain 2）： 120 4. Snai2（Snail family transcriptional repressor 2）： 121 5. Klf9（Krüppel-like factor 9）： 121 6. Klf6（Krüppel-like factor 6）： 121 7. Zfp423（Zinc finger protein 423）： 122 二、親代肥胖在胚胎期與出生後對子代脂肪細胞轉錄調控的影響 122 三、不同技術與細胞模型對候選基因表現的影響 123 四、未來展望 124 第五節 結論 125 總結 126 附圖 127 參考文獻 135 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 母親肥胖 | - |
| dc.subject | 父母雙方肥胖 | - |
| dc.subject | 子代肥胖 | - |
| dc.subject | 白色脂肪組織 | - |
| dc.subject | 脂肪前驅細胞 | - |
| dc.subject | 轉錄因子 | - |
| dc.subject | 單細胞RNA定序 | - |
| dc.subject | maternal obesity | - |
| dc.subject | parental obesity | - |
| dc.subject | offspring obesity | - |
| dc.subject | white adipose tissue | - |
| dc.subject | adipose progenitor cells | - |
| dc.subject | transcription factors | - |
| dc.subject | single-cell RNA sequencing | - |
| dc.title | 親代肥胖改變子代脂肪前驅細胞組成、轉錄體特徵及分化潛力 | zh_TW |
| dc.title | Parental obesity alters the composition, transcriptomic Features, and differentiation potential of offspring adipose progenitor cells | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 114-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 黃青真;謝博軒;王志豪 | zh_TW |
| dc.contributor.oralexamcommittee | Ching-jang Huang;Po-Shiuan Hsieh;Chih-Hao Wang | en |
| dc.subject.keyword | 母親肥胖,父母雙方肥胖子代肥胖白色脂肪組織脂肪前驅細胞轉錄因子單細胞RNA定序 | zh_TW |
| dc.subject.keyword | maternal obesity,parental obesityoffspring obesitywhite adipose tissueadipose progenitor cellstranscription factorssingle-cell RNA sequencing | en |
| dc.relation.page | 144 | - |
| dc.identifier.doi | 10.6342/NTU202600057 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2026-01-15 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科技學系 | - |
| dc.date.embargo-lift | N/A | - |
| 顯示於系所單位： | 生化科技學系 | |
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