請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78754完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蘇剛毅 | |
| dc.contributor.author | Keng-Ieng Wong | en |
| dc.contributor.author | 王璟盈 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:17:01Z | - |
| dc.date.available | 2024-08-28 | |
| dc.date.copyright | 2019-08-28 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-07-23 | |
| dc.identifier.citation | 1. Poirier, P., et al., Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation, 2006. 113(6): p. 898-918.
2. Pi-Sunyer, X., The medical risks of obesity. Postgrad Med, 2009. 121(6): p. 21-33. 3. Basen-Engquist, K. and M.J.C.O.R. Chang, Obesity and Cancer Risk: Recent Review and Evidence. 2011. 13(1): p. 71-76. 4. Hill, J.O., H.R. Wyatt, and J.C. Peters, Energy Balance and Obesity. 2012. 126(1): p. 126-132. 5. Chau, Y.-Y., et al., Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source. Nature Cell Biology, 2014. 16(4): p. 367-375. 6. Wang, W. and P. Seale, Control of brown and beige fat development. Nat Rev Mol Cell Biol, 2016. 17(11): p. 691-702. 7. Choe, S.S., et al., Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. Frontiers in Endocrinology, 2016. 7(30). 8. Boden, G., et al., Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes, 2008. 57(9): p. 2438-44. 9. Özcan, U., et al., Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes. Science, 2004. 306(5695): p. 457-461. 10. Cannon, B. and J. Nedergaard, Brown adipose tissue: function and physiological significance. Physiol Rev, 2004. 84(1): p. 277-359. 11. Ghaben, A.L. and P.E. Scherer, Adipogenesis and metabolic health. Nature Reviews Molecular Cell Biology, 2019. 20(4): p. 242-258. 12. Rosen, E.D. and B.M. Spiegelman, Molecular regulation of adipogenesis. Annu Rev Cell Dev Biol, 2000. 16: p. 145-71. 13. Sarjeant, K. and J.M. Stephens, Adipogenesis. Cold Spring Harb Perspect Biol, 2012. 4(9): p. a008417. 14. Klaus, S., et al., Characterization of the novel brown adipocyte cell line HIB 1B. Adrenergic pathways involved in regulation of uncoupling protein gene expression. J Cell Sci, 1994. 107 ( Pt 1): p. 313-9. 15. Sambeat, A., et al., Epigenetic Regulation of the Thermogenic Adipose Program. Trends Endocrinol Metab, 2017. 28(1): p. 19-31. 16. Lowell, B.B. and B.M. Spiegelman, Towards a molecular understanding of adaptive thermogenesis. Nature, 2000. 404: p. 652. 17. Westerterp, K.R., S.A. Wilson, and V. Rolland, Diet induced thermogenesis measured over 24h in a respiration chamber: effect of diet composition. Int J Obes Relat Metab Disord, 1999. 23(3): p. 287-92. 18. Fontana, L. and L. Partridge, Promoting health and longevity through diet: from model organisms to humans. Cell, 2015. 161(1): p. 106-118. 19. Li, G., et al., Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota. Cell Metabolism, 2017. 26(4): p. 672-685.e4. 20. Pellegrinelli, V., S. Carobbio, and A. Vidal-Puig, Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia, 2016. 59(6): p. 1075-88. 21. Wronska, A. and Z. Kmiec, Structural and biochemical characteristics of various white adipose tissue depots. Acta Physiologica, 2012. 205(2): p. 194-208. 22. Guilherme, A., et al., Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nature reviews. Molecular cell biology, 2008. 9(5): p. 367-377. 23. Bjorndal, B., et al., Different adipose depots: their role in the development of metabolic syndrome and mitochondrial response to hypolipidemic agents. J Obes, 2011. 2011: p. 490650. 24. Misra, A. and N.K. Vikram, Clinical and pathophysiological consequences of abdominal adiposity and abdominal adipose tissue depots. Nutrition, 2003. 19(5): p. 457-466. 25. Ibrahim, M.M., Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev, 2010. 11(1): p. 11-8. 26. Wajchenberg, B.L., Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev, 2000. 21(6): p. 697-738. 27. Bouillaud, F., J. Weissenbach, and D. Ricquier, Complete cDNA-derived amino acid sequence of rat brown fat uncoupling protein. J Biol Chem, 1986. 261(4): p. 1487-90. 28. Symonds, M.E., et al., Adipose tissue and fetal programming. Diabetologia, 2012. 55(6): p. 1597-606. 29. Harms, M. and P. Seale, Brown and beige fat: development, function and therapeutic potential. Nature Medicine, 2013. 19: p. 1252. 30. Lindquist, S. and E.A. Craig, The heat-shock proteins. Annu Rev Genet, 1988. 22: p. 631-77. 31. Vabulas, R.M., et al., Protein folding in the cytoplasm and the heat shock response. Cold Spring Harb Perspect Biol, 2010. 2(12): p. a004390. 32. De Maio, A., Heat shock proteins: facts, thoughts, and dreams. Shock, 1999. 11(1): p. 1-12. 33. Johnson, J.D., et al., Adrenergic receptors mediate stress-induced elevations in extracellular Hsp72. J Appl Physiol (1985), 2005. 99(5): p. 1789-95. 34. Peng, J., et al., An Hsp20-FBXO4 Axis Regulates Adipocyte Function through Modulating PPARgamma Ubiquitination. Cell Rep, 2018. 23(12): p. 3607-3620. 35. Matz, J.M., K.P. LaVoi, and M.J. Blake, Adrenergic regulation of the heat shock response in brown adipose tissue. J Pharmacol Exp Ther, 1996. 277(3): p. 1751-8. 36. Qiu, X.B., et al., The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell Mol Life Sci, 2006. 63(22): p. 2560-70. 37. Tsai, M.F., et al., A new tumor suppressor DnaJ-like heat shock protein, HLJ1, and survival of patients with non-small-cell lung carcinoma. J Natl Cancer Inst, 2006. 98(12): p. 825-38. 38. Liu, Y., et al., HLJ1 is a novel biomarker for colorectal carcinoma progression and overall patient survival. Int J Clin Exp Pathol, 2014. 7(3): p. 969-77. 39. Wang, C.C., et al., Synergistic activation of the tumor suppressor, HLJ1, by the transcription factors YY1 and activator protein 1. Cancer Res, 2007. 67(10): p. 4816-26. 40. Lin, S.Y., et al., HLJ1 is a novel caspase-3 substrate and its expression enhances UV-induced apoptosis in non-small cell lung carcinoma. Nucleic Acids Res, 2010. 38(18): p. 6148-58. 41. Chen, C.H., et al., Acidic stress facilitates tyrosine phosphorylation of HLJ1 to associate with actin cytoskeleton in lung cancer cells. Exp Cell Res, 2010. 316(17): p. 2910-21. 42. Luo, W.J., et al., Novel therapeutic drug identification and gene correlation for fatty liver disease using high-content screening: Proof of concept. Eur J Pharm Sci, 2018. 121: p. 106-117. 43. Froy, O., Metabolism and Circadian Rhythms—Implications for Obesity. Endocrine Reviews, 2010. 31(1): p. 1-24. 44. Jo, H., et al., Endoplasmic reticulum stress induces hepatic steatosis via increased expression of the hepatic very low-density lipoprotein receptor. 2013. 57(4): p. 1366-1377. 45. Liew, C.W., et al., Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance. Nature Medicine, 2013. 19: p. 217. 46. Qiang, G., et al., Transcription regulator TRIP-Br2 mediates ER stress-induced brown adipocytes dysfunction. Scientific Reports, 2017. 7: p. 40215. 47. Lim, S., et al., Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice. Nat Protoc, 2012. 7(3): p. 606-15. 48. Mineo, P.M., et al., Chronic cold acclimation increases thermogenic capacity, non-shivering thermogenesis and muscle citrate synthase activity in both wild-type and brown adipose tissue deficient mice. Comp Biochem Physiol A Mol Integr Physiol, 2012. 161(4): p. 395-400. 49. Aune, U.L., L. Ruiz, and S. Kajimura, Isolation and differentiation of stromal vascular cells to beige/brite cells. J Vis Exp, 2013(73): doi: 10.3791/50191. 50. Braga, M., et al., Follistatin promotes adipocyte differentiation, browning, and energy metabolism. J Lipid Res, 2014. 55(3): p. 375-84. 51. Abe, Y., et al., Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch. Nature Communications, 2018. 9(1): p. 1566. 52. Babicki, S., et al., Heatmapper: web-enabled heat mapping for all. Nucleic acids research, 2016. 44(W1): p. W147-W153. 53. Martinez de Morentin, P.B., et al., Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK. Cell Metab, 2014. 20(1): p. 41-53. 54. Saibil, H., Chaperone machines for protein folding, unfolding and disaggregation. Nature Reviews Molecular Cell Biology, 2013. 14: p. 630. 55. Kim, J.Y., et al., ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P. Cell, 2018. 175(1): p. 133-145.e15. 56. Benito, M., Contribution of brown fat to the neonatal thermogenesis. Biol Neonate, 1985. 48(4): p. 245-9. 57. Ferrannini, G., et al., Genetic backgrounds determine brown remodeling of white fat in rodents. Mol Metab, 2016. 5(10): p. 948-958. 58. Westerberg, R., et al., ELOVL3 is an important component for early onset of lipid recruitment in brown adipose tissue. J Biol Chem, 2006. 281(8): p. 4958-68. 59. Tvrdik, P., et al., Cig30, a mouse member of a novel membrane protein gene family, is involved in the recruitment of brown adipose tissue. J Biol Chem, 1997. 272(50): p. 31738-46. 60. Christian, M., Transcriptional fingerprinting of 'browning' white fat identifies NRG4 as a novel adipokine. Adipocyte, 2015. 4(1): p. 50-4. 61. Cao, W., et al., p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol, 2004. 24(7): p. 3057-67. 62. Busiello, R.A., S. Savarese, and A. Lombardi, Mitochondrial uncoupling proteins and energy metabolism. Frontiers in physiology, 2015. 6: p. 36-36. 63. Fujimoto, T. and R.G. Parton, Not just fat: the structure and function of the lipid droplet. Cold Spring Harbor perspectives in biology. 3(3): p. a004838. 64. Chakravarty, B., et al., Human fatty acid synthase: structure and substrate selectivity of the thioesterase domain. Proc Natl Acad Sci U S A, 2004. 101(44): p. 15567-72. 65. Abe, Y., et al., Histone demethylase JMJD1A coordinates acute and chronic adaptation to cold stress via thermogenic phospho-switch. Nature Communications, 2018. 9(1): p. 1566. 66. Garcia, M.D.C., et al., Regulation of Energy Expenditure and Brown/Beige Thermogenic Activity by Interleukins: New Roles for Old Actors. Int J Mol Sci, 2018. 19(9). 67. Seale, P., et al., Transcriptional control of brown fat determination by PRDM16. Cell Metab, 2007. 6(1): p. 38-54. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78754 | - |
| dc.description.abstract | 肥胖是現時公共衛生上一個嚴峻的議題，肥胖會使人營養不良，令身體出現代謝不平衡的問題。現代社會中人們患上肥胖症大多是由於後天因素影響，生活習慣絮亂、飲良習慣不健康都會導致肥胖症的發生。當吸取過量高脂肪性飲食或高熱量食物時，脂肪及熱量會儲存在白色脂肪細胞內。而減輕體重則可靠棕色脂肪組織會把脂肪消耗掉轉以熱量形式釋放（非顫抖式產熱）。非氈抖式產熱可能受外界環境影響，像是低溫環境可加強產熱，例如當大腦感受到寒冷時交感神經會釋放出去甲腎上腺素(norepinephrine)，其接觸脂肪細胞表面的受體後會活化產熱路徑，像是加快第一型解偶聯蛋白基因(Ucp1)轉錄，增加能量代謝及產熱。HLJ1是DNAJ/HSP40家族的一員，之前已被發現與肝臟脂肪代謝有關，缺乏HLJ1蛋白的小鼠會發展出脂肪肝的情況，在本篇研究中，我們發現HLJ1可能參與在脂肪組織中的產熱活化路徑。在室溫情況下，我們發現缺乏HLJ1的小鼠鼠蹊部白色脂肪(Inguinal White Adipose Tissue)油滴顆粒面積比野生型小鼠的大，且該小鼠負責主要脂肪酸合成的脂肪酸合成酶基因表現量顯著比野生型小鼠高但當小鼠接受低溫刺激七天後，小鼠鼠蹊部白色脂肪HLJ1表現量顯著增加，且缺乏HLJ1小鼠鼠蹊部白色脂肪外觀比野生型小鼠的更顯棕色、油滴顆粒表面積也明顯比較小。更重要的是，產熱標誌基因Ucp1在缺乏HLJ1的小鼠鼠蹊部白色脂肪中明顯上升，在一筆RNA定序的數據也得知該小鼠其他產熱基因表現也上升，代表缺乏HLJ1會增加白色脂肪之產熱能力，因此本研究認為HLJ1在產熱過程中扮演重要角色。 | zh_TW |
| dc.description.abstract | Obesity is a consequence of genetics factor, eating habits, and lifestyle habits-mediated energy imbalance. Body weight gains when energy intake exceeds energy expenditure over a period of time. It is reported that cold induced thermogenesis can re-establish energy balance via burning calories into heat by brown adipocytes or beige adipocytes, and hence ameliorate obesity. HLJ1, a member of DNAJ/Hsp40 co-chaperone, plays a crucial role in unfolded protein response (UPR) system and ER stress. Previously, our group demonstrated HLJ1 was up-regulated in cells with high fat medium treatment and mice deficient in HLJ1 developed impaired lipid metabolism in liver. Our microarray analysis gives us a hint of HLJ1 participating in adipose tissue thermogenesis under cold stress. Under room temperature, iWAT of HLJ1 knockout (KO) mice showed increased expression of Fatty Acid Synthase (Fasn), which meant the KO mice had upregulated adipogenesis. To see whether HLJ1 was involved in adaptive thermogenesis, C57BL/6 and HLJ1-KO mice were divided into either room temperature or cold groups. After one week of cold exposure, elevated thermogenesis and reduced lipid droplets surface were observed in HLJ1-KO mice iWAT compared to WT iWAT. HLJ1 was markedly increased in iWAT of WT mice after cold stress. Body weight of HLJ1-KO mice was obviously reduced and beige selective genes such as Ucp1, Cox7a1 and Cox8b expression was also obviously increased in KO mice iWAT after chronic cold exposure. Taken together, this study indicated that HLJ1 made a contribution in cold induced thermogenesis. It might develop as a potential therapeutic target to treat obesity. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:17:01Z (GMT). No. of bitstreams: 1 ntu-108-R06424003-1.pdf: 5238040 bytes, checksum: 22389eb1f3f423f639e736b3fb419f2f (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 致謝 i
ABSTRACT iii 中文摘要 iv ABBREVIATION v Chapter 1 Introduction 1 1.1 Obesity 2 1.2 Adipogenesis 3 1.3 Thermogenesis 4 1.3.1 Diet-Induced Thermogenesis 4 1.3.2 Cold-Induced Thermogenesis 5 1.4 Adipose Tissue and Adipocytes 5 1.4.1 White Adipose Tissue (WAT) 5 1.4.2 Brown Adipose Tissue (BAT) 6 1.4.3 Brown, Beige and White Adipocytes 7 1.5 Heat Shock Proteins and Thermogenesis 8 1.6 HLJ1 9 Chapter 2 Specific Aims 11 Chapter 3 Materials and Methods 13 3.1 Microarray Analysis and GSEA 14 3.2 Animal Experiments 14 3.3 Cold Exposure to Mice 14 3.4 Body Temperature 15 3.5 Histological Analysis 15 3.6 Lipid Droplets Surface Quantitfication 15 3.7 RNA Extraction and Quantitative PCR 15 3.8 Protein extraction and Western Blotting 16 3.9 Oil Red O Stain 17 3.10 Cell Culture 17 3.11 Isolation of Primary Adipocytes 17 3.12 Adipocytes Differentiation 18 3.13 BAR Activation 18 3.14 RNA Sequencing and Pathway Analysis 18 3.15 Statistical Analysis 19 Chapter 4 Results 20 4.1 GSEA Analysis Revealed the Association between HLJ1 and Thermogenesis 21 4.2 ER Stress was Upregulated in Adipose Tissue of HLJ1-KO Mice 22 4.3 Depletion of HLJ1 Induced iWAT Adipogenesis 22 4.4 HLJ1 Was Highly Expressed in The Process of Adipogenesis 25 4.5 The Establishment of Cold-induced Experimental Model 25 4.6 HLJ1 Was Induced by Chronic Cold Exposure 26 4.7 Reduced Body Weight and Smaller Lipid Droplets Surface Was Identified in HLJ1 Deficient Mice 27 4.8 HLJ1-Ablated Mice iWAT Showed Elevated Thermogenesis After Cold Due to Upregulated Thermogenic Genes Expression 28 Chapter 5 Discussion 32 5.1 HLJ1 was Associated with Adaptive Thermogenesis 33 5.2 HLJ1 Played a Role in Adipogenesis 34 5.3 Adaptive Thermogenesis Was More Activated in KO Mice After Cold 36 Chapter 6 Conclusion 39 Chapter 7 Perspectives and Applications 41 Chapter 8 Figures 43 Chapter 9 Tables 71 REFERENCE 80 | |
| dc.language.iso | en | |
| dc.title | 探討低溫刺激促進脂肪產熱過程中HLJ1所扮演之角色 | zh_TW |
| dc.title | Study of HLJ1 Responses to Adipose Tissue Thermogenesis
Under Cold Exposure | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林亮音,楊雅倩,張以承 | |
| dc.subject.keyword | HLJ1,肥胖症,產熱,白色脂肪組織,冷凍, | zh_TW |
| dc.subject.keyword | HLJ1,obesity,cold,adipose tissue,thermogenesis, | en |
| dc.relation.page | 86 | |
| dc.identifier.doi | 10.6342/NTU201901799 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-07-23 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| dc.date.embargo-lift | 2024-08-28 | - |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-108-R06424003-1.pdf 目前未授權公開取用 | 5.12 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。