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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭柏秀(Po-Hsiu Kuo) | |
| dc.contributor.author | Hung-Hsin Chen | en |
| dc.contributor.author | 陳弘昕 | zh_TW |
| dc.date.accessioned | 2021-06-16T16:16:18Z | - |
| dc.date.available | 2015-03-04 | |
| dc.date.copyright | 2013-03-04 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-02-05 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/62954 | - |
| dc.description.abstract | 本論文試圖用系統、全面性的路徑分析方法研究肥胖及其相關代謝症狀。在中樞神經系統中，POMC和NPY共同在下視丘表現並且調控飲食和能量平衡。除此之外，由腸胃道和胰臟所分泌的荷爾蒙在過往研究中也被發現和下視丘中的能量中樞有交互作用，共同調控食慾和代謝。在本篇研究當中，我們共收集了454位參與者，其中318位的BMI達25以上。我們測量了十種肥胖相關代謝指標，包含腰圍、禁食血糖、飯後血糖、糖化血色素、血壓（收縮壓和舒張壓）和血脂相關指標（三酸甘油脂、高密度膽固醇、低密度膽固醇和總膽固醇量）。遺傳變異的部分，我們分析了四個在POMC和NPY上的單一核甘酸多型性(POMC上的rs2071345、rs1042571 、rs1009388 ； NPY的rs16147)。另外，我們共測定了七種周邊荷爾蒙的禁食後濃度，其中三種來自胰臟（insulin、amylin、pancreatic polypeptide），另外四種分泌自腸胃道（ghrelin、glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and peptide YY）。並試圖利用結構方程模式建構出一完整地從遺傳變異、荷爾蒙表現到代謝指標的模型。在我們建構出的最適模型中，POMC和所有的荷爾蒙表現都有相關，NPY則是和amylin、PP、 ghrelin、 GLP-1、PYY有關，而這兩個基因的變異則主要影響血糖和血脂相關指標。荷爾蒙的部分則以insulin、PP、GIP、GLP-1對代謝指標的影響較為全面。代謝體學研究的部分，我們挑出20對性別、年紀、BMI配對的代謝健康和異常的肥胖者，並且利用液相層析串聯質譜儀分析代謝物濃度；另外多加入了14對配對後的樣本後用氣相層析串聯質譜儀進行分析。三個代謝途徑在代謝健康和異常的肥胖者身上呈現顯著差異的表現（D-glutamine and D-glutamate metabolism、phenylalanine metabolism 、valine, leucine and isoleucine degradation）。在本篇研究中，我們建構出了一個從遺傳變異和荷爾蒙表現到代謝狀況的完整模型，並佐以代謝體學研究的幫助，找出了三個相關的代謝途徑，在肥胖者身上之代謝調控中可能扮演關鍵角色。 | zh_TW |
| dc.description.abstract | Obesity and abnormal metabolic status increase disease burden and mortality worldwide. A systematic view with pathway approach to exam metabolism-regulated pathway is in need. In hypothalamus, Proopiomelanocortin (POMC) and Neuropeptide Y (NPY) play important roles in energy balance, and they regulate appetite and metabolism with pancreatic and gut hormones. Previously, POMC, NPY, pancreatic and gut hormones are found to be correlated with obesity and abnormal metabolic status. In addition, metabolomics studies provide another aspect to investigate the outcome of interests through the whole metabolites screening. In the current study, we aimed to systematically study the correlations and pathways for metabolic outcomes from genes, peripheral hormones, and metabolomics. We recruited 454 participants, in which 318 with BMI≥25. Anthropometrical (e.g. body weight and height, waist circumstance) and biochemical indexes (including systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, total cholesterol, triglyceride, fasting blood glucose, postprandial blood glucose, glycated hemoglobin) were assessed at baseline examination. We genotyped 4 markers (rs2071345, rs1042571 and rs1009388 in POMC gene; rs16147 in NPY gene). Several hormones were measured using fasting blood, including 3 pancreatic hormones: insulin, amylin and pancreatic polypeptide, and 4 gut hormones: ghrelin, glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and peptide YY. Structural equation modeling (SEM) was applied to construct a comprehensive framework from genes, hormones to metabolic phenotypes while adjusted for age, sex, and body-mass index. In our besting fitting model, POMC was associated with all the hormones expression. NPY was associated with amylin, PP, ghrelin, GLP-1 and PYY. Among metabolic traits, both genes mainly exhibited effects on blood glucose and lipid profile. For the effects from hormones to metabolic phenotypes, insulin, PP, GIP and GLP-1 comprehensively affected all aspects of the metabolic traits. Metabolomics study was conducted in 20 sex and age matched metabolic healthy obese (MHO) and 20 metabolic abnormal obese (MAO) individuals using liquid chromatography-mass spectrometer. Additional 14 matched pairs of MHO and MAO samples were further measured by gas chromatography-mass spectrometer. In the metabolomics study, we found that pathways involved with D-glutamine and D-glutamate metabolism, phenylalanine metabolism and valine, leucine and isoleucine degradation are the important pathways to distinguish MHO from MAO individuals. This study is the first to depict the complex pathway in central neuronal functions with genetic variants, pancreatic and gut hormonal expressions for obesity related metabolic traits. With additional metabolomics assessment, important metabolism pathways were also identified for metabolic status in obese subjects. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T16:16:18Z (GMT). No. of bitstreams: 1 ntu-102-R99849043-1.pdf: 1900164 bytes, checksum: d96ed86aa2f70b286cd369b319185c5b (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 口試委員會審定書 I
誌謝 II 中文摘要 III ABSTRACT IV CONTENTS VI TABLE CONTENTS VII FIGURE CONTENTS VIII APPENDIX CONTENTS IX INTRODUCTION 1 I. SYSTEMATIC PATHWAY ESTIMATIONS 1 II. METABOLOMICS STUDY 4 METHODS 7 I. SYSTEMATIC PATHWAY ESTIMATION 7 Subjects 7 Genotyping 7 Measurement of metabolic indexes and hormones 8 Statistical analysis 8 II. METABOLOMICS STUDY 10 Subjects 10 Metabolomics profiling 11 Statistical analysis 12 RESULTS 13 GENETIC ASSOCIATIONS 14 HORMONE EXPRESSION 14 SEM ESTIMATION 15 METABOLOMICS WITH LC-MS 16 METABOLOMICS WITH GC-MS 17 DISCUSSIONS 18 I. SYSTEMATIC PATHWAY ESTIMATION 18 II. METABOLOMICS STUDY 22 III. LIMITATION 26 CONCLUSION 27 ACKNOWLEDGEMENTS 27 REFERENCE 28 TABLES 38 FIGURERS 53 APPENDICES 58 | |
| dc.language.iso | en | |
| dc.subject | 代謝體學 | zh_TW |
| dc.subject | 腸胃道荷爾蒙 | zh_TW |
| dc.subject | 肥胖 | zh_TW |
| dc.subject | 代謝指標 | zh_TW |
| dc.subject | 胰臟荷爾蒙 | zh_TW |
| dc.subject | metabolomics | en |
| dc.subject | obesity-related metabolic trait | en |
| dc.subject | POMC | en |
| dc.subject | NPY | en |
| dc.subject | pancreatic hormone | en |
| dc.subject | gut hormone | en |
| dc.subject | metabolically healthy obesity | en |
| dc.title | 以路徑方法分析肥胖相關代謝指標：從基因、荷爾蒙到代謝體研究 | zh_TW |
| dc.title | Using Pathway Approach to Analyze Obesity-Related Metabolic Traits: From Genetic Variants, Hormone Expressions to Metabolomics | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 潘文涵(Wen-Harn Pan),吳至行(Chih-Hsing Wu) | |
| dc.subject.keyword | 肥胖,代謝指標,胰臟荷爾蒙,腸胃道荷爾蒙,代謝體學, | zh_TW |
| dc.subject.keyword | obesity-related metabolic trait,POMC,NPY,pancreatic hormone,gut hormone,metabolomics,metabolically healthy obesity, | en |
| dc.relation.page | 75 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-02-05 | |
| dc.contributor.author-college | 公共衛生學院 | zh_TW |
| dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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