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系統識別號 U0026-1007201318173000
論文名稱(中文) Imidazoline第一型受體對動物食慾調控之研究
論文名稱(英文) Role of imidazoline I1 receptors in the regulation of food intake in animals
校院名稱 成功大學
系所名稱(中) 基礎醫學研究所
系所名稱(英) Institute of Basic Medical Sciences
學年度 101
學期 2
出版年 102
研究生(中文) 鍾憲輝
研究生(英文) Hsien-Hui Chung
學號 s58951269
學位類別 博士
語文別 英文
論文頁數 85頁
口試委員 指導教授-鄭瑞棠
召集委員-唐一清
口試委員-司君一
口試委員-吳達仁
口試委員-何橈通
口試委員-許朝添
中文關鍵字 尿囊素  食慾  糖尿病  高脂飼料  食慾亢進  肥胖 
英文關鍵字 Allantoin  Appetite  Diabetes  High Fat Diet  Hyperphagia  Obesity 
學科別分類
中文摘要 肥胖是一個常見的代謝性疾病,而食慾在肥胖中扮演很重要的角色。Imidazoline受體對於代謝性疾病有關鍵的影響。因此,本研究目的旨在探討imidazoline受體對於肥胖與食慾之間有何作用。在STZ誘發的糖尿病老鼠動物模式中,我們已發現rilmenidine能減少其食慾亢進的現象以及此作用是藉由活化中樞I1-imidazoline受體去減少神經胜肽Y的表現。此外,在高脂飼料餵食的小鼠中,我們觀察rilmenidine對減少肥胖之效果如何而且發現rilmenidine可經由活化I1-imidazoline受體去降低體重、能量攝取量和減少副睪脂肪的堆積。然而rilmenidine在缺乏瘦素受體的db/db小鼠中無法降低其食慾,此結果顯示rilmenidine須透過瘦素去調控食慾亢進的現象。我們使用尿囊素(allantoin) 當作有效的替代療法去觀察其是否能有效減少肥胖。尿囊素對高脂飼料餵食的小鼠具有降低體重、能量攝取量以及神經胜肽Y的表現。尿囊素亦可減少副睪脂肪的重量及堆積。而尿囊素以上的作用皆透過活化I1-imidazoline受體所導致的。相反,尿囊素在高脂飼料餵食的小鼠中能有效降低血液中高瘦素的含量,但是尿囊素在db/db小鼠中無法降低其能量攝取。此結果暗示著尿囊素可經由活化I1-imidazoline受體達到減肥效果與瘦素的調控有關。因此,活化I1-imidazoline受體後的優點為可藉由調控食慾及減少脂肪堆積來預防肥胖。
英文摘要 Obesity is a well-known metabolic disease in which appetite plays an important role. Imidazoline receptors have a profound influence on metabolic diseases. Thus, the aim of the present study is to investigate the effects of imidazoline receptors on the association between obesity and appetite. We have found that rilmenidine can attenuate hyperphagia in a streptozotocin (STZ)-induced diabetic animal model and that the effect was mediated through the activation of the central imidazoline I1-receptor (I1R) to decrease neuropeptide Y (NPY) expression. Additionally, we investigated how rilmenidine attenuated obesity in high fat diet (HFD)-fed mice and found that rilmenidine decreased body weight, energy intake and epididymal white adipose tissue (eWAT) accumulation via the activation of I1R. However, rilmenidine did not reduce appetite in leptin receptor-deficient db/db mice, which suggests that rilmenidine regulates hyperphagia via leptin. We tested allantoin as an alternative therapy to determine if it could decrease obesity. Allantoin reduced body weight, energy intake and NPY expression in HFD-fed mice. Allantoin also decreased eWAT weight and accumulation. The above effects of allantoin resulted from the activation of I1R. In contrast, allantoin significantly reduced hyperleptinemia in HFD-fed mice, but it could not decrease energy intake in db/db mice. The results suggested that the I1R-mediated obesity-reducing activity of allantoin was associated with the modulation of leptin. Taken together, the activation of I1R has beneficial effects in preventing obesity via the regulation of appetite and the reduction of fat accumulation.
論文目次 Contents
Chinese Abstract……………………………………………………………………………………………I
Abstract…………………………………………………………………………………………………………………III
Acknowledgement………………………………………………………………………………………………VI
Contents…………………………………………………………………………………………………………………VII
Tables………………………………………………………………………………………………………………………X
Figures……………………………………………………………………………………………………………………XI
Abbreviations……………………………………………………………………………………………………XIII
Chapter 1 Introduction……………………………………………………………………………1
1.1. Obesity background…………………………………………………………………2
1.2. Obesity management…………………………………………………………………3
1.3. The role of imidazoline receptors in obesity and appetite…………………………………………………………………………………………………………………4
1.4. Research goals……………………………………………………………………………7
Chapter 2 Materials and methods……………………………………………………8
2.1. Induction of type-1 like diabetes in BALB/c mice……………………………………………………………………………………………………………………………9
2.2. The background of db/db mice………………………………………………9
2.3. Intracerebroventricular (icv) cannulation and injection………………………………………………………………………………………………………………10
2.4. Induction of obesity in HFD-fed mice…………………………11
2.5. Measurement of body weight and energy intake……11
2.6. Measurement of food intake……………………………………………………12
2.7. Measurement of epididymal white adipose tissues……………………………………………………………………………………………………………………12
2.8. Assay of neuropeptide Y (NPY) level……………………………12
2.9. Measurement of leptin levels………………………………………………13
2.10. Histological analysis………………………………………………………………13
2.11. Western blotting analysis……………………………………………………14
2.12. Statistical analysis…………………………………………………………………15
Chapter 3 Results…………………………………………………………………………………………16
3.1. The effect of imidazoline-1 receptor (I1R) activation on STZ-diabetic hyperphagia………………………………………………………………17
3.2. Blockade of imidazoline-1 receptors reversed the rilmenidine-induced effects………………………………………………………………17
3.3. Blockade of cerebral imidazoline-1 receptors reversed the rilmenidine-induced effects……………………………………………………17
3.4. The role of α2-adrenoceptors in activity of rilmenidine in STZ-diabetic mice…………………………………………………………………………………18
3.5. Chronic effect of rilmenidine on hyperphagia of diabetic mice……………………………………………………………………………………………………18
3.6. Changes of neuropeptide Y (NPY) levels in the hypothalamus from STZ-diabetic mice…………………………………………19
3.7. Effect of imidazoline I1-receptor (I1R) activation on body weight in HFD-fed mice………………………………………………………………19
3.8. Involvement of imidazoline I1-receptors in the rilmenidine-induced reduction of energy intake……………19
3.9. Decreased expression of imidazoline receptors in the hypothalamus of HFD-fed mice……………………………………………………………20
3.10. Improvement of epididymal white adipose tissue (eWAT) by rilmenidine in HFD-fed mice………………………………………………………20
3.11. Effect of rilmenidine in db/db mice…………………………21
3.12. Effect of allantoin on body weight in HFD-fed mice……………………………………………………………………………………………………………………………21
3.13. Improvement of epididymal white adipose tissue (eWAT) induced by allantoin in HFD-fed mice………………………………………21
3.14. Involvement of imidazoline I1-receptors in the allantoin-induced reduction of energy intake…………………22
3.15. Changes of neuropeptide Y (NPY) levels in the hypothalamus of HFD-fed mice……………………………………………………………22
3.16. Effect of allantoin in db/db mice………………………………22
3.17. The improvement of hyperleptinemia induced by allantoin in HFD-fed mice……………………………………………………………………23
Chapter 4 Discussion…………………………………………………………………………………24
Chapter 5 Conclusion…………………………………………………………………………………32
References……………………………………………………………………………………………………………34
Tables………………………………………………………………………………………………………………………44
Figures……………………………………………………………………………………………………………………49
Publication list……………………………………………………………………………………………64
Appendixes……………………………………………………………………………………………………………68
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