臺灣博碩士論文加值系統

本研究主要探討在高脂低醣飲食中，以魚油取代部分油脂，對大鼠脂質代謝及體重的影響。
本次研究可分為兩個實驗，實驗一以 32 隻五週齡雄性 Sprague Dawley (SD) 大鼠進行實驗，共分為四組，(1) 正常控制組 (Normal control, NC)、(2) 高脂低醣組 (High-fat, low carbohydrate diet, LC)、(3) 含 5% 魚油之高脂低醣組 (LC 以 5% fish oil 取代 lard, 5CF)、(4) 含 10% 魚油之高脂低醣組 (LC 以 10% fish oil 取代 lard, 10CF)，實驗進行 11 週。結果顯示，含魚油之高脂低醣飲食可能透過 α-MSH (α-melanocyte-stimulating hormone) 的上升來抑制食慾，且 5CF 組減緩體重上升的效果較 10CF 組佳。魚油會顯著降低高脂低醣飲食所導致的脂肪組織堆積及脂肪組織分泌之 leptin。在脂質代謝方面，魚油顯著降低血液 TC、TG 及肝臟 TG，透過肝臟組織切片亦可看到魚油顯著降低肝臟脂肪空泡，改善脂質代謝異常，但魚油會顯著增加肝臟脂質過氧化物 TBARS 之濃度，且 10CF 組顯著高於 5CF 組，因此探討選用 5CF 組做為魚油組，以進行續實驗。
實驗二以 28 隻五週齡雄性 SD 大鼠進行實驗，共分為四組，(1) 正常控制組 (NC)、(2) 高脂組 (High-fat diet, HF)、(3) 高脂低醣組 (LC)、(4) 含 5% 魚油之高脂低醣組 (5CF)，實驗進行 11 週。結果顯示，高脂飲食可能透過抑制 ghrelin 降低食慾，高脂低醣飲食則以 α-MSH 抑制食慾。空腹體重 HF 組顯著重於 NC 組，但與 LC、5CF 組無顯著差異。脂質代謝方面魚油顯著降低血脂、肝臟 TC、脂肪空泡堆積，改善脂質代謝異常，且減少脂肪組織堆積。魚油會顯著增加抗氧化酵素 SOD、GPx 活性，降低發炎因子 TNF-α。綜上所述，高脂飲食與高脂低醣飲食調控食慾的激素不盡相同，含魚油之高脂低醣飲食可能是透過 α-MSH 的上升來抑制食慾，且 5% 魚油比 10% 魚油更有效的降低食慾，減緩體重上升，且體內過氧化情形較輕微，魚油還可以通過降低血脂、肝臟脂質堆積和脂肪空泡來改善高脂低醣飲食引起的脂質代謝異常。

This study mainly explored the effect of replacing part of fat with fish oil in a high-fat and low carbohydrate diet on lipid metabolism and body weight in rats.
This study can be divided into two experiments. Experiment one was conducted with 32 five-week-old male Sprague Dawley (SD) rats, divided into four groups, (1) normal control diet (NC), (2) high-fat, low carbohydrate diet (LC), (3) high-fat, low carbohydrate diet containing 5% fish oil (LC replaces lard, 5CF with 5% fish oil), (4) high-fat, low carbohydrate diet containing 10% fish oil (LC replaces lard, 10CF with 10% fish oil), the experiment was carried out for 11 weeks. The results showed that the high-fat and low carbohydrate diet containing fish oil may suppress appetite through the increase of α-MSH (α-melanocyte-stimulating hormone), and the 5CF group has a better effect on reducing weight gain than the 10CF group. Fish oil significantly reduces adipose tissue accumulation caused by a high-fat and low carbohydrate diet, and the secretion of leptin from adipose tissue is also reduced. In terms of lipid metabolism, fish oil significantly reduces blood TC, TG and liver TG. Through liver tissue slices, it can also be seen that fish oil significantly reduces liver lipids, fatty vacuoles and improves lipid metabolism abnormalities, but fish oil significantly increases liver lipid The concentration of peroxide TBARS, and the 10CF group was significantly higher than the 5CF group, so the 5CF group was selected as the fish oil group for subsequent experiments.
Experiment two was conducted with 32 five-week-old male SD rats, divided into four groups, (1) normal control diet (NC), (2) high-fat diet (HF), (3) high-fat and low carbohydrate diet (LC), (4) high-fat and low carbohydrate containing 5% fish oil diet (5CF), the experiment was carried out for 11 weeks. The results showed that the high-fat diet may reduce appetite by suppressing ghrelin, and there was no significant difference in the final body weight between the four groups. In terms of lipid metabolism, fish oil significantly reduces blood lipids, liver TC, fatty vacuole accumulation, improves lipid metabolism abnormalities, and reduces adipose tissue accumulation. Fish oil significantly increases the activity of antioxidant enzymes SOD and GPx, and reduces the inflammatory factor TNF-α. In summary, high-fat diet and high-fat low-sugar diet have different appetite regulation hormones. High-fat low-sugar diets containing fish oil may suppress appetite through the increase of α-MSH, and 5% fish oil is more effective than 10% fish oil. It reduces appetite, slows weight gain, and has milder peroxidation in the body. Fish oil can also reduce abnormal lipid metabolism by reducing blood lipids, liver lipid accumulation and fatty vacuoles.

第壹章、 前言 1
第貳章、 文獻整理 2
第一節、 肥胖症 (Obesity) 2
1. 現況與定義 2
2. 肥胖與脂肪組織之關聯性 3
(1) 脂肪組織 3
(2) 肥胖和脂肪細胞分化的調控 4
3. 肥胖與脂肪細胞激素 4
(1) 腫瘤壞死因子 - α (Tumor Necrosis Factor alpha, TNF-α) 4
(2) 介白素 - 6 (Interleukin-6, IL-6) 5
第二節、 高脂低醣飲食 5
1. 介紹 5
2. 高脂飲食對脂質代謝之影響 6
第三節、 食慾相關激素 6
1. 瘦素 (Leptin) 6
2. 膽囊收縮素 (Cholecystokinin, CCK) 7
3. 飢餓素 (Ghrelin) 7
4. α - 黑色素細胞刺激素 (α-Melanocyte-stimulating hormone, α-MSH) 7
第四節、 脂質代謝 8
1. 脂質代謝相關酵素 8
(1) 荷爾蒙敏感性脂解酶 (Hormone-sensitive lipase, HSL) 8
(2) 脂蛋白脂解酶 (Lipoprotein lipase, LPL) 8
(3) 乙醯輔酶 A 羧化酶 (Acetyl-CoA carboxylase, ACC) 8
(4) 脂肪酸合成酶 (Fatty acid synthase, FAS) 9
第五節、 脂質過氧化 9
1. 脂質過氧化物生成過程 9
2. 酵素性抗氧化防禦系統 10
(1) 超氧化物歧化酶 (superoxide dismutase, SOD) 10
(2) 麩胱甘肽過氧化物酶 (Glutathione peroxidase, GPx) 10
第六節、 膳食魚油 10
1. 定義 10
2. 魚油對脂質代謝之影響 11
(1) 魚油對血漿中三酸甘油酯之影響 11
(2) 魚油對血漿中膽固醇之影響 11
3. 魚油對體內抗發炎之作用 12
第參章、 實驗設計 13
第一節、 實驗動機 13
第二節、 實驗一 14
1. 實驗流程 14
2. 分析項目 15
第三節、 實驗二 16
1. 實驗流程 16
2. 分析項目 17
第肆章、 實驗材料 18
第一節、 實驗動物 18
第二節、 實驗飼料 18
第三節、 實驗樣品 18
第四節、 實驗儀器 19
第伍章、 實驗方法 20
第一節、 脂肪酸組成分析 20
1. 脂肪酸萃取 20
2. 脂肪酸之分析 20
第二節、 動物分組 21
1. 實驗一 21
2. 實驗二 21
第三節、 動物飼養與樣品收集 22
1. 實驗一 22
2. 實驗二 22
第四節、 飼料配方 23
第五節、 樣品分析 25
1. 血漿 25
(1) 血漿中總膽固醇濃度分析 (TC) 25
(2) 血漿中三酸甘油酯濃度分析 (TG) 25
(3) 血漿中 AST、ALT 活性分析 25
(4) 血漿中 ALP 活性分析 26
(5) 血漿中尿酸濃度分析 (Uric acid) 26
(6) 血漿中肌酸酐濃度分析 (Creatinine) 26
(7) 血漿中尿素氮濃度分析 (Blood Urea Nitrogen, BUN) 27
(8) 血漿中腫瘤壞死因子 α 濃度分析 (TNF-α) 27
(9) 血漿中介白素 - 6 濃度分析 (IL-6) 27
(10) 血漿中瘦素濃度分析 (Leptin) 27
(11) 血漿中膽囊收縮素濃度分析 (CCK) 27
(12) 血漿中 α - 黑色素細胞刺激素濃度分析 (α-MSH) 28
(13) 血漿中飢餓素濃度分析 (Ghrelin) 28
(14) 血漿中 ß - 羥基丁酸濃度分析 (beta-hydroxybutyrate) 28
(15) 血漿中脂蛋白含量分析 (Lipoprotein) 28
(16) 血漿中過氧化物質含量分析 (Plasma TBARS) 28
2. 肝臟 29
(1) 肝臟脂質萃取 29
(2) 肝臟總膽固醇與三酸甘油酯含量分析 29
(3) 肝臟過氧化物質含量分析 (Liver TBARS) 29
(4) 肝臟細胞質液製備 30
(5) 肝臟細胞質液蛋白質濃度測定 31
(6) 肝臟乙醯輔酶 A 羧化酶活性測定 (ACC) 31
(7) 肝臟脂肪酸合成酶活性測定 (FAS) 32
(8) 肝臟中葡萄糖-6-磷酸去氫酶活性分析 (G6PD) 32
(9) 肝臟中超氧化物歧化酶活性分析 (SOD) 33
(10) 肝臟中穀胱甘肽過氧化酶活性分析 (GPx) 33
3. 組織脫水包埋、切片與染色 34
(1) 組織脫水 34
(2) 組織包埋 34
(3) 石蠟切片 34
(4) 組織染色 34
4. 脂肪組織 35
(1) 脂肪組織脂質萃取 35
(2) 脂肪組織三酸甘油酯含量分析 35
(3) 荷爾蒙敏感性脂解酶速率分析 (HSL) 35
(4) 脂蛋白脂解酶速率分析 (LPL) 36
5. 腸道分析 36
(1) 小腸黏膜蒐集 36
(2) 小腸雙醣酶活性測定 37
6. 糞便 37
(1) 糞便濕重與乾重 37
(2) 糞便脂質萃取 37
(3) 糞便總膽固醇與三酸甘油酯含量測定 38
7. 統計分析 38
第陸章、 結果 39
第一節、 實驗一 39
1. 大白鼠之體重變化、攝食量和食物利用率 39
2. 大白鼠之組織臟器重量 39
3. 大白鼠之血漿生化指標測定 39
(1) 血漿中脂質濃度 39
(2) 血漿中 AST、ALT、ALP 活性 40
(3) 血漿中 ß - hydroxybutyrate、TBARS 濃度 40
(4) 血漿中 Leptin、α-MSH、CCK 濃度 40
4. 大白鼠之肝臟生化指標測定 40
(1) 肝臟中脂質濃度及脂質生合成酵素活性 40
(2) 肝臟組織切片 H&E 染色之脂肪空泡面積 40
(3) 肝臟 TBARS 濃度 41
5. 大白鼠之腎周及副睪脂肪組織脂質含量 41
6. 大白鼠之糞便重量及脂質濃度 41
第二節、 實驗二 41
1. 大白鼠之體重變化、攝食量和食物利用率 41
2. 大白鼠之組織臟器重量 41
3. 大白鼠之血漿生化指標測定 42
(1) 血漿中脂質濃度 42
(2) 血漿中 AST、ALT、ALP 活性與 TNF-α、IL-6 濃度 42
(3) 血漿中 ß – hydroxybutyrate、TBARS 濃度 42
(4) 血漿中 Leptin、α-MSH、CCK、Ghrelin 濃度 42
(5) 血漿中 Uric acid、Creatinine、BUN 濃度 43
4. 大白鼠之肝臟生化指標測定 43
(1) 肝臟脂質濃度 43
(2) 肝臟脂質生合成酵素活性 43
(3) 肝臟組織切片 H&E 染色中脂肪空泡面積 43
(4) 肝臟中 TBARS 濃度與抗氧化酵素活性 43
5. 大白鼠之脂肪組織生化指標測定 44
(1) 腎周及副睪脂肪組織脂質含量 44
(2) 腎周脂肪組織脂解速率與 LPL 活性 44
6. 大白鼠小腸黏膜雙醣酶活性 44
7. 大白鼠糞便重量及脂質濃度 44
8. 大白鼠尿液 ß – hydroxybutyrate 濃度 44
9. 實驗飼料之脂肪酸分析 45
第柒章、 討論 46
第一節、 實驗一 46
1. 含魚油之高脂低醣飲食對大鼠體重、食慾、組織臟器之影響 46
(1) 體重及食慾之影響 46
(2) 肝臟、脂肪組織、小腸及肌肉組織之影響 46
2. 含魚油之高脂低醣飲食對大鼠脂質代謝之影響 47
(1) 血漿、肝臟脂質代謝之影響 47
(2) 脂肪組織代謝之影響 47
(3) 糞便脂質代謝之影響 47
3. 含魚油之高脂低醣飲食對大鼠肝功能之影響 48
4. 含魚油之高脂低醣飲食對大鼠脂質過氧化之影響 48
第二節、 實驗二 49
1. 含魚油之高脂低醣飲食對大鼠體重、食慾、組織臟器之影響 49
(1) 體重、食慾之影響 49
(2) 肝臟、脂肪組織之影響 49
2. 含魚油之高脂低醣飲食對大鼠脂質代謝之影響 50
(1) 血漿、肝臟脂質代謝之影響 50
(2) 脂肪組織代謝之影響 50
(3) 糞便脂質代謝之影響 50
3. 含魚油之高脂低醣飲食對大鼠肝、腎功能及發炎因子之影響 51
(1) 肝、腎功能之影響 51
(2) 發炎因子之影響 51
4. 含魚油之高脂低醣飲食對大鼠脂質過氧化之影響 51
5. 含魚油之高脂低醣飲食對大鼠醣類代謝之影響 52
第三節、 綜合討論 52
第捌章、 結論 54
第玖章、 參考文獻 57

圖目錄
圖 一、實驗期間大白鼠之體重變化 66
圖 二、攝取不同實驗飼料十一週後之大白鼠血漿 ß-羥基丁酸含量 67
圖 三、攝取不同實驗飼料十一週後之大白鼠血液和肝臟 TBARS 濃度 68
圖 四、攝取不同實驗飼料十一週後之大白鼠血漿 Leptin 含量 69
圖 五、攝取不同實驗飼料十一週後之大白鼠血漿 α-MSH 含量 70
圖 六、攝取不同實驗飼料十一週後之大白鼠血漿 CCK 含量 71
圖 七、攝取不同實驗飼料十一週後之大白鼠肝臟脂質生合成酵素活性 72
圖 八、攝取不同實驗飼料十一週後，大白鼠肝臟組織切片圖 73
圖 九、攝取不同實驗飼料十一週後之大白鼠腎周和副睪脂肪組織脂質含量 74
圖 十、實驗期間大白鼠之體重變化 75
圖 十一、攝取不同實驗飼料十一週後之大白鼠血漿 TNF-α 和 IL-6 濃度 76
圖 十二、攝取不同實驗飼料十一週後之大白鼠尿液和血漿 ß-羥基丁酸含量 77
圖 十三、攝取不同實驗飼料十一週後之大白鼠血液和肝臟 TBARS 濃度 78
圖 十四、攝取不同實驗飼料十一週後之大白鼠血漿 Leptin 含量 79
圖 十五、攝取不同實驗飼料十一週後之大白鼠血漿 α-MSH 含量 80
圖 十六、攝取不同實驗飼料十一週後，大白鼠血漿 CCK 含量 81
圖 十七、攝取不同實驗飼料十一週後之大白鼠血漿 Ghrelin 含量 82
圖 十八、攝取不同實驗飼料十一週後之大白鼠肝臟脂質生合成酵素活性 83
圖 十九、攝取不同實驗飼料十一週後之大白鼠肝臟組織切片圖 84
圖 二十、攝取不同實驗飼料十一週後之大白鼠肝臟抗氧化酵素活性 85
圖 二十一、攝取不同實驗飼料十一週後之大白鼠腎周和副睪脂肪組織脂質含量 86
圖 二十二、攝取不同實驗飼料十一週後之大白鼠腎周脂肪組織脂解速率變化及脂蛋白脂解酶活性 87
圖 二十三、攝取不同實驗飼料十一週後之大白鼠小腸雙醣酶活性 88



表目錄
表 一、攝取不同實驗飼料十一週後大白鼠之體重及攝食量 89
表 二、攝取不同實驗飼料十一週後之大白鼠臟器重量 90
表 三、攝取不同實驗飼料十一週後之大白鼠血漿脂質含量 91
表 四、攝取不同實驗飼料十一週後之大白鼠 AST、ALT、ALP 活性 92
表 五、攝取不同實驗飼料十一週後之大白鼠肝臟脂質含量 93
表 六、攝取不同實驗飼料十一週後之大白鼠糞便重量、總膽固醇及三酸甘油酯濃度 94
表 七、攝取不同實驗飼料十一週後大白鼠之體重及攝食量 95
表 八、攝取不同實驗飼料十一週後之大白鼠臟器重量 96
表 九、攝取不同實驗飼料十一週後之大白鼠血漿脂質含量 97
表 十、攝取不同實驗飼料十一週後之大白鼠 AST、ALT、ALP 活性 98
表 十一、攝取不同實驗飼料十一週後之大白鼠血漿尿酸、肌酸酐及尿素氮含量 99
表 十二、攝取不同實驗飼料十一週後之大白鼠肝臟脂質含量 100
表 十三、攝取不同實驗飼料十一週後之大白鼠糞便重量、總膽固醇及三酸甘油酯濃度 101
表 十四、實驗飼料之脂肪酸組成 102

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