Search

高膽固醇血症是產生動脈粥樣硬化的危險因素，本研究旨在探討甾醇的氧化產物和植物化學物質在餵食高膽固醇食金黃地鼠模型中對脂蛋白代謝的影響及其相關機制。, 本研究包含四個部分。食物中同時含有植物甾醇及其氧化產物。第一部分旨在研究β-穀甾醇（Si）、甾醇(St)、β-穀甾醇氧化產物(SiOP)和豆甾醇氧化產物(StOP)對金黃地鼠血脂的影響。本研究顯示，Si和St組能有效降低血總膽固醇（TC）、非高密度脂蛋白膽固醇（non-HDL-C）和甘油三酯（TAG）的水平，而SiOP和StOP則失去此能力。RT-PCR分析表明，Si和St而非SiOP和StOP，能下調腸道醯基輔酶A：膽固醇醯基轉移酶2（ACAT2）和微粒體甘油三酯轉移蛋白（MTP）的mRNA表達。Si和St而非SiOP和StOP能有效防止動脈粥樣硬，Si和St的動脈弓舒張能力強於對照組和SiOP、StOP組。, 辣椒鹼是辣椒中的活性成分。本研究第二部分表明，辣椒鹼能降低TC，NON-HDL-C，TAG，而不影響高密度脂蛋白膽固醇。餵養辣椒鹼能增加糞便中總酸性固醇的排泄，此作用有可能是通過上調膽固醇7α-羥化酶（CYP7A1）和下調肝X受體α（LXRα）的基因表達來實驗。辣椒鹼可通過抑制COX-2基因表達來改善內皮依賴性收縮。, 藍莓含有豐富的抗炎抗氧化劑，例如花青素。本研究第三部分表明，食物中添加0.5和1.0藍莓花青素能導致TC呈劑量效益地降低6-12%，其中還伴隨22-29的中性固醇和41-74%的膽汁酸排泄的增加。RT-PCR分析表明食物中添加的藍莓花青素能下調腸道Niemann-Pick C1 Like 1 (NPC1L1)，ACAT2，MTP， 腺苷三磷酸結合盒轉運體G8(ABCG8)和肝臟3-羥基-3-甲基戊二醯輔酶A還原酶(HMG-CoA Reductase)的基因表達。, 芝麻素是芝麻種子中含有抗氧化活性的木脂素類化合物。本研究第四部分表明，在食物中添加芝麻素可有效調控TC和non-HDL-C，同時不影響TAG，並導致非高密度脂蛋白膽固醇與高密度脂蛋白膽固醇比例的下降。這有可能與膽汁酸排泄增加、CYP7A1基因的上調，LXR的下調有關。, 綜上所述，本研究證實了植物甾醇、辣椒鹼、藍莓花青素和芝麻素降低血膽固醇的能力。與此同時，本研究還表明植物甾醇被氧化後將失去其降低膽固醇的能力。, Hypercholesterolemia is a major risk factor in the development of atherosclerosis. Functional foods that can lower or regulate cholesterol concentration are of interest to both public and scientific communities. The present study was to investigate the effects of phytosterols, phytosterol oxidation products (POPs), capsaicinoids, blueberry anthocyanins and sesamin on plasma cholesterol concentration using hamsters as a model., The whole project consisted of four parts. Human diets contain both phytosterols and POPs. Part I was to examine the effect of β-sitosterol (Si), stigmasterol (St), β-sitosterol oxidation products (SiOP) and stigmasterol oxidation products (StOP) on plasma cholesterol concentration. Results showed both Si and St could reduce while SiOP and StOP lost the capacity of lowering plasma total cholesterol (TC), non-high density lipoprotein cholesterol (non-HDL-C) and triacylglycerols (TAG). Real-Time PCR analysis demonstrated Si and St but not SiOP and StOP down-regulated mRNA levels of intestinal acyl CoA: cholesterol acyltransferase 2 (ACAT2) and microsomal triglyceride protein (MTP). In addition, aortas from hamsters given diets containing Si and St relaxed better than those from the control and their corresponding SiOP- and StOP-treated hamsters, suggesting that Si and St not SiOP and StOP were beneficial in improving lipoprotein profile and aortic function., Capsaicinoids refer to a group of pungent compounds that are the active components found in chili peppers. Part II was to investigate the cholesterol-lowering activity of capsaicinoids and the associated molecular mechanisms. Results demonstrated that capsaicinoids reduced plasma TC, non-HDL-C and TAG with high-density lipoprotein cholesterol (HDL-C) being unaffected. This was accompanied by an increase in the fecal excretion of total acidic sterols, possibly mediated by up-regulation of cholesterol 7α-hydroxylase (CYP7A1) and down-regulation of liver X receptor alpha (LXRα). Capsaicinoids could also improve the endothelium-dependent relaxations and reduce the endothelium-dependent contractions by inhibiting the gene expression of COX-2., Blueberries are rich in anthocyanins. Results from Part III experiments demonstrated that dietary supplementation with 0.5 and 1.0 % blueberry anthocyanins for 6 weeks decreased plasma TC concentration by 6-12% in a dose-dependent manner. This was accompanied by increasing the excretion of fecal neutral and acidic sterols by 2229% and 4174%, respectively. Real-time PCR analyses demonstrated that incorporation of blueberry anthocyanins into diet down-regulated the genes of intestinal Niemann-Pick C1-like 1 (NPC1L1), ACAT2, MTP, ABCG 8 and hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase., Sesamin is a major lignan in sesame seed and is known to exhibit antioxidative activity. Part IV was to investigate the mechanism by which sesamin decreased plasma cholesterol concentration. Results clearly demonstrated supplementation of sesamin into diets could favorably reduce serum TC and non-HDL-C with TAG being unaffected. In addition, dietary supplementation of 0.2 or 0.5% of sesamin could cause a significant decrease in the ratio of non-HDL-C to HDL-C. This was accompanied by a marked increase in bile acid excretion and up-regulation of CYP7A1 and down-regulation of LXRα., In conclusion, phytosterols, capsaicinoids, blueberry anthocyanins and sesamin were beneficial in improving lipoprotein profile in hamsters fed a high-cholesterol diet. However, phytosterols lose the cholesterol-lowering capacity when they are oxidized., Detailed summary in vernacular field only., Liang, Yintong., Thesis (Ph.D.)--Chinese University of Hong Kong, 2012., Includes bibliographical references (leaves 112-123)., s also in Chinese., Chapter Chapter 1 --- General Introduction, Chapter 1.1 --- Cardiovascular diseases --- p.1, Chapter 1.2 --- Cholesterol --- p.2, Chapter 1.3 --- Lipoproteins --- p.4, Chapter 1.4 --- Cholesterol homeostasis --- p.6, Chapter 1.4.1 --- HMG-CoA reductase --- p.7, Chapter 1.4.2 --- LDL receptor --- p.9, Chapter 1.4.3 --- Intestine ACAT2 --- p.10, Chapter 1.4.4 --- NPC1L1 --- p.11, Chapter 1.4.5 --- CYP7A1 and LXRα --- p.12, Chapter 1.4.6 --- SREBP2 --- p.14, Chapter 1.4.7 --- ABCG5 and ABCG8 --- p.15, Chapter 1.5 --- Phytochemicals --- p.16, Chapter 1.5.1 --- Phytosterols --- p.16, Chapter 1.5.2 --- Capsaicinoids --- p.17, Chapter 1.5.3 --- Blueberry anthocyanins --- p.19, Chapter 1.5.4 --- Sesamin --- p.20, Chapter 1.6 --- Animal model --- p.22, Chapter Chapter 2 --- Effect of Phytosterols and their Oxidation Products on Lipoprotein Profiles and Vascular Function, Chapter 2.1 --- Introduction --- p.23, Chapter 2.2 --- Objective --- p.24, Chapter 2.3 --- Materials and methods --- p.24, Chapter 2.3.1 --- Preparation of sitosterol oxidation products (SiOP) and stigmasterol oxidation products (StOP), Chapter 2.3.2 --- Diets --- p.25, Chapter 2.3.3 --- Hamsters --- p.25, Chapter 2.3.4 --- Analysis of individual SiOP and StOP in serum and liver --- p.26, Chapter 2.3.5 --- Analysis of plasma lipoproteins --- p.28, Chapter 2.3.6 --- Measurement of atherosclerotic plaque --- p.28, Chapter 2.3.7 --- Analysis of cholesterol in the liver and aorta --- p.28, Chapter 2.3.8 --- Determination of fecal neutral and acidic sterols --- p.29, Chapter 2.3.9 --- Real-time PCR analysis of mRNA of liver SREBP2, LDL receptor, HMG-CoA reductase, CYP7A1, LXRα, and small intestine NPC1L1, ABCG5, ABCG8, ACAT2, MTP. --- p.29, Chapter 2.3.10 --- Western blotting analysis of hepatic SREBP2, LDL receptor, HMG-CoA reductase, LXRα and CYP7A1 --- p.32, Chapter 2.3.11 --- Vascular reactivity --- p.32, Chapter 2.4 --- Results --- p.34, Chapter 2.4.1 --- Composition of SiOP and StOP --- p.34, Chapter 2.4.2 --- Food intake, body and organ weights --- p.34, Chapter 2.4.3 --- Plasma TC, HDL, non-HDL ,TAG, Non-HDL-C/HDL-C --- p.34, Chapter 2.4.4 --- Aortic cholesterol and atherosclerotic plaque --- p.35, Chapter 2.4.5 --- Liver cholesterol, SiOP and StOP --- p.35, Chapter 2.4.6 --- Fecal neutral, acidic sterols and cholesterol balance --- p.35, Chapter 2.4.7 --- Immunoblot and mRNA analysis --- p.36, Chapter 2.4.8 --- Vascular reactivity --- p.36, Chapter 2.4.9 --- Role of COX in endothelium-dependent contractions --- p.37, Chapter 2.5 --- Discussion --- p.50, Chapter Chapter 3 --- Cholesterol-Lowering Activity of Capsaicinoids Is Mediated by Increasing Sterol Excretion in Hamsters Fed a High Cholesterol Diet, Chapter 3.1 --- Introduction --- p.54, Chapter 3.2 --- Objective --- p.55, Chapter 3.3 --- Materials and methods --- p.55, Chapter 3.3.1 --- Diets --- p.55, Chapter 3.3.2 --- Hamsters --- p.57, Chapter 3.3.3 --- Analysis of plasma lipoproteins --- p.57, Chapter 3.3.4 --- Measurement of atherosclerotic plaque --- p.57, Chapter 3.3.5 --- Analysis of cholesterol in the liver and aorta --- p.57, Chapter 3.3.6 --- Determination of fecal neutral and acidic sterols --- p.57, Chapter 3.3.7 --- Real-time PCR analysis of mRNA of liver SREBP2, LDL receptor, HMG-CoA reductase, CYP7A1, LXRα, and small intestine NPC1L1, ABCG5, ABCG8, ACAT2, MTP --- p.57, Chapter 3.3.8 --- Western blotting analysis of hepatic SREBP2, LDL receptor, HMG-CoA reductase, LXRα and CYP7A1 --- p.58, Chapter 3.3.9 --- Vascular reactivity --- p.58, Chapter 3.4 --- Results --- p.59, Chapter 3.4.1 --- Food intake, body and organ weights --- p.59, Chapter 3.4.2 --- Plasma TC, HDL, non-HDL,TAG, Non-HDL-C/HDL-C --- p.59, Chapter 3.4.3 --- Aortic cholesterol and atherosclerotic plaque --- p.59, Chapter 3.4.4 --- Fecal neutral, acidic sterols and cholesterol balance --- p.59, Chapter 3.4.5 --- Immunoblot and mRNA analysis --- p.60, Chapter 3.4.6 --- Vascular reactivity --- p.60, Chapter 3.4.7 --- Role of COX in endothelium-dependent contractions --- p.61, Chapter 3.5 --- Discussion --- p.74, Chapter Chapter 4 --- Effect of Blueberry Anthocyanins on Lipoprotein Profiles in Hamsters Fed a Cholesterol Diet, Chapter 4.1 --- Introduction --- p.77, Chapter 4.2 --- Objective --- p.78, Chapter 4.3 --- Materials and methods --- p.78, Chapter 4.3.1 --- HPLC analysis of blueberry anthocyanins --- p.78, Chapter 4.3.2 --- Diet --- p.79, Chapter 4.3.3 --- Hamsters --- p.80, Chapter 4.3.4 --- Analysis of plasma lipoproteins --- p.80, Chapter 4.3.5 --- Analysis of cholesterol in the liver --- p.80, Chapter 4.3.6 --- Determination of fecal neutral and acidic sterols --- p.81, Chapter 4.3.7 --- Real-time PCR analysis of mRNA of liver SREBP2, LDL Receptor, HMG-CoA Reductase, CYP7A1, LXRα, and small intestine NPC1L1, ABCG5, ABCG8, ACAT2, MTP --- p.81, Chapter 4.3.8 --- Western blotting analysis of hepatic SREBP2, LDL Receptor, HMG-CoA reductase, LXRα and CYP7A1 --- p.81, Chapter 4.4 --- Results --- p.82, Chapter 4.4.1 --- Food intake, body, and organ weights --- p.82, Chapter 4.4.2 --- Plasma TC, HDL-C, non-HDL-C, and TAG --- p.82, Chapter 4.4.3 --- Liver cholesterol concentration --- p.82, Chapter 4.4.4 --- Fecal total sterols and apparent sterol retention --- p.82, Chapter 4.4.5 --- Immunoblot and mRNA analysis --- p.83, Chapter 4.5 --- Discussion --- p.92, Chapter Chapter 5 --- Effect of Sesamin on Lipoprotein Profiles in Hamsters Fed a high Cholesterol Diet, Chapter 5.1 --- Introduction --- p.95, Chapter 5.2 --- Objective --- p.95, Chapter 5.3 --- Materials and methods --- p.96, Chapter 5.3.1 --- Diets --- p.96, Chapter 5.3.2 --- Hamsters --- p.96, Chapter 5.3.3 --- Methods --- p.97, Chapter 5.4 --- Results --- p.98, Chapter 5.4.1 --- Food intake, body and organ weights --- p.98, Chapter 5.4.2 --- Plasma TC, HDL-C, non-HDL-C ,TAG, Non-HDL-C/HDL-C --- p.98, Chapter 5.4.3 --- Liver cholesterol --- p.98, Chapter 5.4.4 --- Fecal neutral, acidic sterols and cholesterol balance --- p.98, Chapter 5.4.5 --- Immunoblot and mRNA analysis --- p.99, Chapter 5.5 --- Discussion --- p.109, References --- p.112, http://library.cuhk.edu.hk/record=b5549462, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Cardiovascular disease (CVD) is a major health problem in developed countries and, with increasing prevalence in developing countries and Eastern Europe. Due to the increased incidence with advancing age, there is a need to develop primary preventive interventions to prolong the period of healthy life. Diet has a substantial influence on health and aging. The composition of the human diet plays an important role in the management of lipid and lipoprotein. In this respect, we have focused on the effects of two kinds of functional foods, tea seed oil and dietary onion on their hypocholesterolemic activities and underlying mechanisms in the present study., Clearly, there are many claims on health benefits of Alliums , however, most, with the exception of garlic, have not received any rigorous or even gentle scientific investigation. Thus, the present study was carried out to explore hypocholesterolemic effects of onion supplementation. After fed for 2 weeks of the high fat high cholesterol diet, thirty-six 8-week male hamsters were divided into four groups. Control group was continued fed with high fat high cholesterol diet, while the other two experimental groups were fed control diet plus 1% (1OP) and 5% (5OP) onion powder for 8 weeks. It was found that feeding high dose of onion powder diet significantly prevented the increase in serum TC, Non-HDL-C and the ratio of non-HDL-C/HDL respectively in hamsters fed a 0.1% cholesterol diet. In contrast, the ratio of HDL/TC in high dose group was significantly increased than that in the control. Low onion dose group tended to have the similar effects as high dose group but, statistically, no difference was observed between the control and low dose groups. Besides, both doses of onion powder diets could significantly countered the increase in serum TG levels. High dose of onion supplementation tended to increase output of fecal neutral and acidic sterols, resulting in reduction of cholesterol retained and absorption. High dose of onion powder diet could significantly up- regulate SREBP-2, LXRbeta, and CYP7A1 protein expressions. The hypocholesterolemic activities of onion might due to the richness in alkyl and alkenyl sulfoxide compounds, anthocyanin, quercetin and cycloalliin, all of which have therapeutic effects., In conclusion, diet plays an important role in reducing the risk of CVD. This has led to the search for specific foods and food components that may help to improve the serum lipoprotein profile. In present study, tea seed oil and onion was proved to help favorably modify the plasma lipoprotein profile, serving as health supplementation. However, their potential mechanisms were not fully studied and need to be further explored., Interest in tea seed oil (named tea oil) as a cooking oil is increasing. However, its effect on blood cholesterol is not known. This study was therefore conducted to compare the hypocholesterolemic activity of tea oil with grape seed, canola and corn oils. Fifty 8-week-old male hamsters were first fed a high fat diet (5% lard), and supplemented with 0.1% cholesterol for 2 weeks and then divided into five groups. Control group was continuously fed high fat high cholesterol diet, while the experimental groups were fed high fat, high cholesterol diet plus 10% tea oil, grape seed oil, canola oil and corn oil for 12 weeks. Results showed that plasma total cholesterol (TC), non-HDL-cholesterol (non-HDL-C) and triacylglycerols (TG) in hamsters fed a 0.1% cholesterol diet containing tea, grape, canola or corn oil was significantly reduced compared with those in lard-fed group. Tea oil decreased only non-HDL-C and had no or little effect on HDL-C concentration, while grape oil reduced both. Besides, tea oil-fed hamsters excreted less neutral but greater acidic sterols compared with other three oils. Unlike grape oil, tea oil up-regulated sterol regulatory element binding protein (SREBP-2) and LDL receptor. Differences between tea oil and the tested vegetable oils could be attributable partially to >80% oleic acid in tea oil., Guan, Lei., Adviser: Chung Hau Yin., Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: ., Thesis (Ph.D.)--Chinese University of Hong Kong, 2010., Includes bibliographical references (leaves 98-125)., Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web., Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web., also in Chinese., isbn: 9781124497778, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Grape seed proanthocyanidins (GSP) as a cholesterol-lowering nutraceutical has been investigated in both humans and animals, however, little is known of how it interacts with the genes and proteins involved in lipoprotein metabolism in vivo. So the first objective of the present study was to investigate the effect of GSP supplementation on blood cholesterol level and gene expression of cholesterol-regulating enzymes in Golden Syrian hamsters maintained on a 0.1% cholesterol diet., Hypercholesterolemia is one of the major proven risk factors for atherosclerosis. Decreasing blood total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels with cholesterol-lowering nutraceuticals and dietary intake modification could slow or reverse the progression of cardiovascular disease., In conclusion, the present study confirmed that hypocholesterolemic activity of GSP was most likely mediated by enhancement of bile acid excretion and up-regulation of CYP7A1. The present study also demonstrated that frequent cholesterol and myristic acid intake is associated with elevation of plasma TC level, while beta-sitosterol intake frequency had no effect on plasma cholesterol for a given amount., In the beta-sitosterol consumption frequency study, hamsters fed the basal diet with a gavage-administration of 3 mg cholesterol 3 times (control), or a gavage-administration of 3 mg beta-sitosterol with 3 mg cholesterol 3 times per day (high beta-sitosterol intake frequency), or a gavage-administration of 9 mg beta-sitosterol with 3 mg cholesterol for one time and 3 mg cholesterol for the other two times (low beta-sitosterol intake frequency). The results demonstrated that for a given dose of beta-sitosterol, the administration frequency had no or little effect on plasma lipoprotein profiles. The present study also found that cholesterol-lowering activity of beta-sitosterol was mediated by its inhibition on the intestinal cholesterol absorption with up-regulation of NPC1L1, ATP binding cassette transporters G5 and G8 (ABCG5/8) and MTP., In the cholesterol consumption frequency study, hamsters were given daily 9 mg of cholesterol either in diet (high cholesterol intake frequency) or a gavage-administration of 3 times 3 mg (regular cholesterol intake frequency) and 1 time 9 mg (low cholesterol intake frequency). The results demonstrated that there was an increasing trend in concentrations of plasma TC, Non-HDL-C, TC/HDL-C ratio and TG in association with the cholesterol intake frequency. It is the first time to demonstrate that the increasing cholesterol intake frequency increased the apparent cholesterol absorption. Elevation of plasma TC and cholesterol absorption is most likely mediated by up-regulation of intestinal Niemann-Pick C1-like 1 (NPC1L1), acyl coenzyme A: cholesterol acyltransferase 2 (ACAT2), and microsomal triacylglycerol transport protein (MTP) gene expression., In the myristic acid consumption frequency study, hamsters were given daily 210 mg of myristic acid either in diet (high myristic acid intake frequency) or a gavage-administration of 3 times 70 mg (regular myristic acid intake frequency) and 1 time 210 mg (low myristic acid intake frequency). The results showed that the increasing consumption frequency elevated plasma TC, Non-HDL-C and HDL-C levels. Elevation of plasma TC and HDL-C is most likely mediated by up-regulation of NPC1L1 and down-regulation of scavenger receptor BI (SR-BI) gene expression via enhancement of dietary myristic acid absorption., The results affirmed supplementation of 0.5% or 1.0% GSP could decrease plasma TC, non-high density lipoprotein cholesterol (Non-HDL-C) and triglyceride (TG) levels. In addition, dietary GSP was able to increase the excretion of bile acids by 3--4 folds, this was partially mediated by up-regulation of Cholesterol 7 alpha-hydroxylase (CYP7A1) in both transcriptional and translational levels. It was concluded that the hypocholesterolemic activity of GSP was most likely mediated by enhancement of bile acid excretion and up-regulation of CYP7A1., The second objective of the present study was to investigate the effect of cholesterol, myristic acid and beta-sitosterol consumption frequency on plasma lipoprotein profiles in hamsters. Numerous studies reported that dietary cholesterol and saturated fatty acids elevated plasma TC level, whereas dietary phytosterols in moderate and high doses favorably reduced plasma TC and LDL levels. However, it is still unknown whether consumption frequency of sterols and fatty acids could affect plasma cholesterol level and lipid profiles., Jiao, Rui., Adviser: Chen Zhen Yu., Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: ., Thesis (Ph.D.)--Chinese University of Hong Kong, 2010., Includes bibliographical references (leaves 123-150)., Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web., Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web., also in Chinese., isbn: 9781267003713, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)