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. / Abstract also in Chinese.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344704 |
| Date | January 2010 |
| Contributors | Jiao, Rui., Chinese University of Hong Kong Graduate School. Division of Life Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xv, 150 leaves : ill.) |
| Rights | 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/) |
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