請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69562
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 楊寧蓀(Ning-Sun Yang) | |
dc.contributor.author | Yung-Tsung Chen | en |
dc.contributor.author | 陳詠宗 | zh_TW |
dc.date.accessioned | 2021-06-17T03:19:22Z | - |
dc.date.available | 2018-07-23 | |
dc.date.copyright | 2018-07-23 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-06-27 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69562 | - |
dc.description.abstract | 肥胖在已開發國家及開發中國家為常見之疾病。許多疾病常伴隨著肥胖而發生,例如慢性發炎以及非酒精性脂肪肝。然而,目前對於肥胖及非酒精性脂肪肝之療效仍需更進一步的探討與改善。許多文獻指出於肥胖及非酒精性脂肪肝病症中,腸道菌群扮演著重要的角色,而利用益生菌改變腸道菌相可有效改善肥胖症狀。然而探討益生菌可否藉由改變腸道菌群並減緩非酒精性脂肪肝及其影響之機制仍未清楚了解;除此之外,結合益生菌與控制飲食攝取於調節肥胖腸道菌群及其代謝物影響之研究相當稀少。先前的研究結果已證實,糖液克菲爾所分離之馬利乳酸桿菌APS1具有許多益處,其中包括可有效抑制高脂飼糧誘導肥胖小鼠之影響。因此,本研究目的為探討糖液克菲爾APS1菌株對於高脂飼糧誘導大鼠非酒精性脂肪肝之影響以及探討結合APS1菌株與低脂飲食於已肥胖小鼠是否可促進改善肥胖之影響。於本實驗結果我們發現餵食APS1菌株可調節高脂飼糧誘導肥胖大鼠腸道菌相,減少與非酒精性脂肪肝相關之特定菌群和降低體增重,且可增加肝臟組織中SIRT-1/Nrf-2轉錄因子活性及調控下游與脂質代謝和氧化壓力相關分子路徑,降低肝臟脂質累積及增加肝臟抗氧化活性。而結合APS1菌株與低脂飲食可改善肥胖腸道菌群,促進增加已肥胖小鼠之體減重及降低體脂肪堆積。此外,餵食APS1菌株可調節脂質代謝相關之血清代謝物和腸道荷爾蒙表現以及增加糞便中短鏈脂肪酸丁酸表現量。本研究動物實驗結果可證實,糖液克菲爾分離之APS1菌株可調節宿主腸道微生物體,增加血清中腸道荷爾蒙及糞便中短鏈脂肪酸之表現,促進肝臟組織SIRT-1/Nrf-2蛋白質活性表現而降低肝臟脂質形成與堆積,且可改善宿主血清中與脂質代謝相關之代謝物表現。最後,本研究結果提供科學證據證明馬利乳酸桿菌APS1具改善代謝症候群之潛力益生菌,未來可應用於機能性食品開發。 | zh_TW |
dc.description.abstract | To date, obesity is a widespread disease in developing and developed countries. Some syndromes are accompanied with obesity, such as low grade inflammation and non-alcoholic fatty liver disease (NAFLD). Currently, there are no approved clinical treatment for non-alcoholic fatty liver disease and the difficulty of long-term management has produced a high rate of failure for obesity patients. Therefore, improving the efficacy of obesity and NAFLD treatment is a significant goal. A number of studies indicate that gut microbiota dominates and plays an important role in obesity and non-alcoholic fatty liver disease. Using probiotics to manipulate the gut microbiota has been as the potential approach for improving obesity. However, it remains unclear whether the probiotic can ameliorate the non-alcoholic fatty liver through manipulating the gut microbiota, in addition, the study on the effect of combination of probiotics and diet control in the regulation of obesity-related gut microbiota and metabolites is quite rare. In our previous studies, Lactobacillus mali APS1 (APS1), which is isolated from sugary kefir, has been demonstrated to confer several health benefits in vivo, including amelioration of high-fat diet (HFD)-induced obesity in mice. Therefore, this study aimed to investigate the effect of APS1 on high-fat diet-induced NAFLD and the efficacy of a combination of APS1 and dieting on improvement of obesity in vivo. The results showed that APS1 manipulated the gut microbiota, resulting in reducing the abundance of specific NAFLD-associated bacteria, and significantly reduced hepatic lipid accumulation and increased hepatic antioxidant activity by regulating SIRT-1/Nrf-2 signaling pathway in HFD-fed rats. The combination of APS1 and dieting accelerated body weight loss and reduced fat accumulation though manipulating obesity-associated gut microbiota in preexisting obese mice. Additionally, APS1 intervention modulated the lipid metabolism-associated metabolites, appetitive hormones and increased fecal butyric acid concentration. In conclusion, this study highlighted that APS1 strain isolated from sugary kefir regulating the host gut microbiota and inducing the expressions of short-chain fatty acids and intestinal hormones resulted in reduction of body fat accumulation and hepatic steatosis in vivo. This study provided scientific evidences to show that Lactobacillus mali APS1 can be the potential probiotic to improve metabolic disorder syndrome in the application of functional food. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T03:19:22Z (GMT). No. of bitstreams: 1 ntu-107-D99642008-1.pdf: 10754437 bytes, checksum: 6ab4c78557e877f93d7ae8876722295c (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii Abstract iii Introduction 1 Chapter 1: Literature review 3 1.1 Lipid mobilization of obesity 3 1.2 Pathology of NAFLD 6 1.3 The current treatments of obesity and NAFLD 9 1.4 Gut microbiome in obesity and NAFLD 11 1.5 Gut microbiota-targeted treatment with probiotics 15 1.6 Lactobacillus mali APS1 18 1.7 Aims of study 20 Chapter 2: Investigation of the effect of L. mali APS1 on hepatic steatosis in HFD-induced obese rats 23 2.1 Introduction 23 2.2 Material and methods 24 2.2.1 APS1 preparation 24 2.2.2 Animal 24 2.2.3 Experimental protocol 24 2.2.4 Analysis of serum biochemical marker and short chain fatty acid concentration 25 2.2.5 Histological analysis 26 2.2.6 Immunohistochemistry 26 2.2.7 Western blot analysis 27 2.2.8 Hepatic oxidative enzymes and triglyceride analysis 27 2.2.9 DNA extraction and gut microbiota analysis 28 2.2.10 Statistical analysis 28 2.3 Results 29 2.3.1 APS1 intervention prevented the features of obesity and NAFLD progression 29 2.3.2 APS1 intervention modulated the glucose level and HOMA-IR with increasing GLP-1 and butyrate levels 33 2.3.3 APS1 intervention mediated SIRT-1 activity 34 2.3.4 APS1 intervention suppressed hepatic oxidation stress by the induction of Nrf-2 expression 36 2.3.5 APS1 intervention changed the NAFLD-associated gut microbiota composition in HFD-fed rats 38 2.4 Discussion 43 2.5 Conclusions 46 Chapter 3: Investigation of the effect of the combination of L. mali APS1 and dieting on the efficacy of obesity treatment in preexisting obese mice. 48 3.1 Introduction 48 3.2 Material and methods 49 3.2.1 Bacterial strain 49 3.2.2 Animal experimental protocol 49 3.2.3 Analysis of serum biochemistry and satiety hormones 50 3.2.4 Analysis of fecal SCFAs 50 3.2.5 Histological analysis 50 3.2.6 Western blot analysis 51 3.2.7 Analysis of hepatic triglyceride 51 3.2.8 DNA extraction and sequencing of gut microbiota 52 3.2.9 Analysis of serum metabolomic profile 53 3.2.10 Analysis of the correlation between the gut microbiome and specific metabolites 54 3.2.11 Generation of GFP-expressing APS1 54 3.2.12 Intestinal location of GFP-APS1 by immunofluorescence analysis 55 3.2.13 Statistical analysis 55 3.3 Results 56 3.3.1 APS1 accelerated body weight loss, reduced caloric intake, and lowered fat mass in obese mice on a diet 56 3.3.2 APS1 ameliorated hepatic steatosis in preexisting obese mice after dieting 60 3.3.3 APS1 manipulated obesity-associated gut microbiota in preexisting obese mice after dieting 62 3.3.4 APS1 affected fecal SCFAs excretion and expression of satiety hormones in preexisting obese mice after dieting 70 3.3.5 APS1-regulating metabolites contributed to accelerating weight loss in preexisting obese mice after dieting 72 3.4 Discussion 76 3.5 Conclusion 80 Conclusion 82 References 84 | |
dc.language.iso | en | |
dc.title | 馬利乳酸桿菌APS1對高脂飼糧誘導肥胖與非酒精性脂肪肝疾病動物模式之腸道菌相調節與機理研究 | zh_TW |
dc.title | The mechanistic study of Lactobacillus mali APS1 on manipulation of gut microbiome in high-fat diet-induced obesity and non-alcoholic fatty liver disease animal model | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 博士 | |
dc.contributor.coadvisor | 陳明汝(Ming-Ju Chen) | |
dc.contributor.oralexamcommittee | 劉?睿,楊三連,廖?成,潘子明,李宣書 | |
dc.subject.keyword | 腸道菌相,馬利乳酸桿菌APS1,非酒精性脂肪肝,肥胖,短鏈脂肪酸, | zh_TW |
dc.subject.keyword | gut microbiota,Lactobacillus mali APS1,non-alcoholic fatty liver disease,obesity,short chain fatty acids, | en |
dc.relation.page | 114 | |
dc.identifier.doi | 10.6342/NTU201801119 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-06-27 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物科技研究所 | zh_TW |
顯示於系所單位: | 生物科技研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-107-1.pdf 目前未授權公開取用 | 10.5 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。