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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃國晉 | zh_TW |
| dc.contributor.advisor | Kuo-Chin Huang | en |
| dc.contributor.author | 林玟玓 | zh_TW |
| dc.contributor.author | Wen-Ti Lin | en |
| dc.date.accessioned | 2024-08-26T16:23:25Z | - |
| dc.date.available | 2024-08-27 | - |
| dc.date.copyright | 2024-08-26 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-08-02 | - |
| dc.identifier.citation | 1. Powell EE, Wong VW-S, Rinella M. Non-alcoholic fatty liver disease. The Lancet 2021;397(10290):2212-2224.
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"Value of traditional noninvasive fibrosis models in diagnosis of significant liver fibrosis in patients with chronic hepatitis B and metabolic associated fatty liver disease." 临床肝胆病杂志 39.9 (2023): 2110-2116. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/95039 | - |
| dc.description.abstract | 非酒精性脂肪肝(non-alcoholic fatty liver disease)目前是全世界最常見的肝臟疾病，盛行率約為 25-40%，其定義為在無過量酒精攝取的情形下，肝臟出現脂肪沉積的情形，是代謝症候群(metabolic syndrome)的肝臟表徵。非酒精性脂肪肝的疾病範疇包括單純肝臟脂肪沉積、非酒精性脂肪肝炎、肝纖維化及肝硬化。隨著疾病的進展，非酒精性脂肪肝炎病人有較高的機會發展成肝纖維化及肝硬化，並有較高之心血管及癌症死亡率。
肝臟脂肪代謝途徑包括游離脂肪酸攝取、肝臟脂肪新生(hepatic De novo lipogenesis)、氧化及分泌。肝臟細胞脂肪累積主要來源是游離脂肪酸攝取及脂肪新生。研究顯示於非酒精脂肪肝病人中，三酸甘油酯累積的與肝臟脂肪新生增強有極為密切的關係，游離脂肪酸攝取、氧化及分泌減少占的角色較小。健康的成人中，肝臟內生脂肪占比在空腹時約為 5%，進食後約為 26%。而在非酒精性脂肪肝的成人中，肝臟脂肪新生在空腹時就已經增速了，無明顯空腹進差別，平均約為 23%。 S14 (the Spot 14, thyroid response Spot 14, Thrsp)蛋白質，為一肝臟細胞激素(hepatokine)及強內生脂肪生成刺激物，其位於人類的 S14 基因座落於第 11 對染色體的長鏈上(11q13.5)。 S14 mRNA 大量表現於老鼠脂肪合成組織如肝臟、白色及粽色脂肪細胞與泌乳之乳腺上皮細胞，與脂肪合成有密切之關聯。動物研究顯示 S14 基因剔除老鼠，脂肪合成相關酵素活性降低、肝組織三酸甘油酯含量較少、空腹血糖值及葡萄糖耐受性較佳。相反的， S14 基因轉染(transfection)之小鼠其肝臟三酸甘油酯的含量及內生脂肪合成酵素的表現增加。人類體外脂肪細胞培養研究顯示，禁食 48 小時後肥胖病人之 S14 mRNA 表現較非肥胖病人較高，顯示肥胖病人皮下組織之 S14 mRNA 似乎較不受禁食所抑制。另一研究呈現了不同的結果，發現肥胖病人之內臟細肪細胞之 S14 mRNA 表現量與身體質量指數、體脂量、腰臀比及收縮壓呈負相關，Yenting Chen 等人亦發現人類血清 S14 與心血管代謝危險因子呈負相關。然後，目前仍未有人類 S14 非酒精性脂肪肝之研究，由於內生脂肪合成增加是造成非酒精性脂肪肝的主要原因之一，我們假設，可以調控肝臟脂肪新生的 S14 在非酒精性脂肪肝的病生理機轉扮演了重要的角色。本文目的為探討人類血清 S14 非酒精性脂肪肝之相關性。 本研究計畫以血清中之 S14 檢體為研究項目，採新竹社區招募了 614 位受試者。收集其血清 S14 及性別、體重、身體質量指數、體脂肪率、血糖、糖化血色素、血紅素、血脂肪、胰島素、肝臟細胞激素等相關項目。我們依據有無非酒精性脂肪肝將受試者分組。脂肪肝之有無及嚴重程度以肝臟半定量臟超音波Ultrasonographic Fatty Liver Indicator (US-FLI)評估。我們以 S14 濃度酵素免疫分析法去測定血清 S14 值。最後的結果以迴歸分析探討血清 S14 濃度與非酒精性脂肪肝的相關性。 在我們的實驗中，有 52.2%的受試者患有非酒精性脂肪肝。我們發現，有脂肪肝之受試者有較高之血清 S14 值，且較高之血清 S14 值與較嚴重之脂肪肝呈正相關。我們依 S14 濃度將受試者分三組，相較於 S14 最低之組別，於校正後干擾因子後，患有較嚴重脂肪肝之勝算比在次高組為 1.22 (95%信賴區間：0.78-1.92)，在最高組為 2.08 (95%信賴區間：1.28-3.39)。與過去研究一致，本研究亦發現血清 S14 值與心血管代謝因子呈負相關。我們推測，隨著脂肪累積及心血管代謝因子逐漸發展，S14 的負迴饋機制被啟動導致了這一結果。在個體長期過量的脂肪累積後，脂肪生成基因會逐漸減少表現，目的為限制脂肪細胞的過度肥大與進一步之積累，包括脂肪肝的形成。過去研究亦支持我們的假設，即在肥胖病人的脂肪細胞中，與脂肪合成及分化相關之因子包括 SREBP-1c、FASN、ACC、 PEPCK、ATP Citratelyase 及 Pyruvate Carboxylase 被顯著抑制。另外，雖然非酒精性脂肪肝與代謝症候群有許多相似的病生理機轉，目前無直接證據表明此一負回饋機制在非酒精性脂肪肝與代謝症候群一樣發生。在我們的研究中，血清 S14 值與脂肪肝呈正相關，但又與心血管代謝因子呈負相關，我們猜測此一 S14 的負回饋抑制在非酒精性脂肪肝之病人被抑制或受損，亦有可能被 S14R 救援。S14R 為與 S14 分子結構 32%相同之蛋白質，亦伴演著強脂肪新生刺激物之角色，相較於S14 分布與許多組織，S14R 其主要分佈於肝細胞。由於我們的血清 S14 酵素免疫分析法亦會偵測到 S14R，未來需要進一步研究去闡明與釐清 S14R 所伴演之角色。綜合以上結果，本研究以半定量超音波及人體血清 S14 濃度的酵素免疫分析法，探討社區民眾非酒精性脂肪肝與血清 S14 值之相關性。我們發現人體 S14 血清濃度與心血管代謝因子呈負相關，但與脂肪肝呈顯著正相關。這些結果皆與前人的動物或人類研究相呼應。至於為何人體血清 S14 濃度與心血管代謝因子及脂肪肝之相關性呈現相反的結果，我們猜測，非酒精性脂肪肝病人之脂肪新生負回饋反應受損或遭到 S14R 的救援。然後更詳細的機制還需要後續更多的研究並發展出人體血清 S14 濃度的單株抗體酵素免疫分析法來證實於闡釋。 | zh_TW |
| dc.description.abstract | Background
S14 has been identified as a potent stimulator of de novo hepatic lipogenesis (DNL) in rodents. However, it is unclear how S14 is regulated in humans with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between serum S14 and liver steatosis in humans with NAFLD. Materials and methods A total of 614 participants were recruited from community. Liver steatosis were evaluated according to the Ultrasonographic Fatty Liver Indicator (US-FLI), which is a semiquantitative liver ultrasound score. Anthropometric and biochemical indices were collected for further analysis. The risk of liver steatosis severity was estimated by a cumulative logistic regression model. Results NAFLD was found in 52.2% of the participants. The subjects with NAFLD showed higher levels of waist circumference, body mass index, insulin resistance, aspartate aminotransferase, dyslipidemia, visceral fat, serum S14 and risk of metabolic syndrome (MetS) than those of controls. Compared with the first tertile of serum S14, the odds ratios for the risk of more severe liver steatosis were 1.22 (95%confidence interval [CI]: 0.78–1.92) for those of the second tertile and 2.08 (95% CI: 1.28–3.39) for the third tertile (P for trend< 0.05) after adjusting for confounding factors. Conclusions Higher serum S14 level was not only found in NAFLD subjects but also was positively correlated with the severity of liver steatosis. S14 may play an important role in the mechanism of DNL for NAFLD in humans. | en |
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| dc.description.provenance | Made available in DSpace on 2024-08-26T16:23:25Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員審定書 i
誌謝 ii 中文摘要 iii 英文摘要 vi 目次 viii 圖次 x 表次 xi 縮寫 xii 第一章 緒論 1 第一節 背景與文獻回顧 1 第二節 臨床檢查與診斷評估 6 第三節 致病病理機轉 10 第四節 S14的發現與分佈 18 第五節 研究假說與特定目的 23 第二章 研究方法與材料 25 第一節 受試者的選取與臨床實驗室檢查 25 第二節 統計分析 28 第三章 結果 29 第一節 主要觀察結果 29 第二節 血清S14值與代謝因子之相關性 29 第四章 討論 31 第一節 S14與脂肪肝及脂肪新生之已發表文獻 31 第二節 本研究之S14與非酒精性脂肪肝疾病之關聯 31 第三節 研究限制與優點 33 第五章 未來展望 34 參考文獻 35 圖 61 表 63 附錄 66 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | S14 (the Spot 14 | zh_TW |
| dc.subject | thyroid response Spot 14 | zh_TW |
| dc.subject | Thrsp) | zh_TW |
| dc.subject | 非酒精性脂肪肝(non-alcoholic fatty liver disease) | zh_TW |
| dc.subject | 肝臟脂肪新生 (hepatic De novo lipogenesis) | zh_TW |
| dc.subject | 代謝症候群(metabolic syndrome) | zh_TW |
| dc.subject | 肝臟半定量臟超音波(Ultrasonographic Fatty Liver Indicator (US-FLI)) | zh_TW |
| dc.subject | ultrasonographic fatty liver indicator(US-FLI) | en |
| dc.subject | metabolic syndrome | en |
| dc.subject | S14 (the Spot 14 | en |
| dc.subject | thyroid response Spot 14 | en |
| dc.subject | Thrsp) | en |
| dc.subject | non-alcoholic fatty liver disease | en |
| dc.subject | hepatic De novo lipogenesis | en |
| dc.title | 血清S14濃度與非酒精性脂肪肝之相關性研究 | zh_TW |
| dc.title | Elevated serum S14 levels are associated with more severe liver steatosis by ultrasonography | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 楊偉勛;陳祈玲 | zh_TW |
| dc.contributor.oralexamcommittee | Wei-Shiung Yang;Chi-Ling Chen | en |
| dc.subject.keyword | S14 (the Spot 14, thyroid response Spot 14, Thrsp),非酒精性脂肪肝(non-alcoholic fatty liver disease),肝臟脂肪新生 (hepatic De novo lipogenesis),代謝症候群(metabolic syndrome),肝臟半定量臟超音波(Ultrasonographic Fatty Liver Indicator (US-FLI)), | zh_TW |
| dc.subject.keyword | S14 (the Spot 14, thyroid response Spot 14, Thrsp),non-alcoholic fatty liver disease,hepatic De novo lipogenesis,metabolic syndrome,ultrasonographic fatty liver indicator(US-FLI), | en |
| dc.relation.page | 72 | - |
| dc.identifier.doi | 10.6342/NTU202402428 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2024-08-05 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 臨床醫學研究所 | - |
| 顯示於系所單位： | 臨床醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-112-2.pdf 未授權公開取用 | 5.83 MB | Adobe PDF |
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