Regulation of Sterol Transport by Dietary Phytosterol Esters

LDL cholesterol is associated with the development of atherosclerosis and is therefore considered an important target for intervention to prevent cardiovascular diseases. The inhibition of cholesterol absorption in the small intestine is an attractive approach to lowering plasma cholesterol, one that is exploited by drug therapy as well as dietary supplementation with plant sterols. The mechanism of action of plant sterol esters (PSE) is still incompletely understood, therefore this study was conducted to test the hypothesis that hydrolysis of plant sterol esters is necessary for their cholesterol-lowering effects to be realized. Male Syrian hamsters were fed diets containing no PSE, PSE containing stearic acid, palmitic acid, oleic acid or plant sterol ethers containing stearic acid. Treatment compounds were added at 5% of the diet (g/g). Diets were high is cholesterol and saturated fat to induce hyperlipidemia. The treatments effectively created a spectrum of PSE hydrolysis across which cholesterol metabolism could be compared. Stearate ethers, Stearate Esters and Palmitate Esters were poorly hydrolyzed (1.69-4.12%), while oleate sters were hydrolyzed at 88.29%, and cholesterol absorption correlated negatively with percent hydrolysis with a correlation coefficient of-0.8504. These results suggest that PSE hydrolysis plays a necessary role in the cholesterol-lowering effects of PSE. In addition, these data also suggest that poorly hydrolyzed plant sterol esters may act through an alternative mechanism than that of competition with cholesterol for micelle incorporation. We suggest that these PSE that are not well hydrolyzed may lower cholesterol by forming an oil phase into which cholesterol is solubilized making it unavailable for absorption into enterocytes. In summary, our results demonstrated that PSE hydrolysis is necessary for cholesterol-lowering. Additionally, poorly hydrolyzed PSE may function through an alternative pathway than micelle competition with cholesterol. iv Acknowledgements DR. TIMOTHY CARR Thank you for supporting my research and my education these past two years. I recognize your willingness to give of your time and energies as I had need, and I do not take your sacrifice lightly. I count it an honor to have been trained by a superior researcher and professor. Thank you for the countless hours you have spent training me in laboratory practice and imparting sound research philosophy. Apart from your efforts, a graduate education of the caliber that I have received would not have been possible. Perhaps the greatest acknowledgement belongs to my wife who has been with for the duration of my academic pursuits, and has played an …