Determination of synthesis and absorption of cholesterol: Influence of apo E polymorphism, dietary cholesterol, and dietary fatty acids

Abstract

The main emphasis of this project was to determine parameters of cholesterol metabolism, in particular those pertaining to the synthesis and absorption of cholesterol, and how these parameters are affected by dietary cholesterol and different fatty acids. Whether the individual response is influenced by apo E polymorphism was also investigated. During a screening program detecting apo E polymorphisms, 53 healthy students with the phenotypes E3/2 [n = 6], E4/2 [n = 5], E3/3 [n = 22], and E4/3 [n = 20] were selected. The influence of dietary cholesterol and various fatty acids on serum lipids and other laboratory parameters for estimating cholesterol synthesis and absorption was determined in a nine week controlled dietary trial. Serum levels of the cholesterol precursors lathosterol and desmosterol were determined, serving as indicators of endogenous cholesterol synthesis. The quantitative examination of these two compounds showed that serum lathosterol levels changed markedly during the study whereas the concentration of serum desmosterol did not vary significantly. The high cholesterol diet led to a highly significant increase in the level of serum lathosterol. Adherence to a diet, enriched in monounsaturated fatty acids, resulted in a significant decrease in serum lathosterol. Therefore, the observed influence of dietary cholesterol and monounsaturated fatty acids on serum cholesterol may be explained, at least in part, by changes in endogenous cholesterol synthesis. Serum concentrations of the phytosterols campesterol and b-sitosterol were taken as indicators for the efficiency of cholesterol absorption. These parameters showed only slight changes that were not obviously related to the intake of dietary cholesterol or of different fatty acids. Although individual responses due to various fatty acids and cholesterol in the diet could be observed, no clear correlation with apo E polymorphism could be established for this phenomenon. In addition, no differences between the apo E phenotypes were found regarding the parameters of cholesterol synthesis and absorption examined in this trial.

Zusammenfassung

Untersuchungen zum Cholesterinstoffwechsel werden in der Regel unter Einsatz von Isotopen [7] oder mit Hilfe aufwendiger Bilanzmethoden durchgeführt [11]. Neuere Erkenntnisse weisen auf die Bedeutung des Gehaltes an Cholesterinvorstufen im Serum als Maß für die Cholesterinbiosynthese hin [2]. Der Phytosteringehalt im Serum kann dagegen als Maß für die Effizienz der Cholesterinabsorption gewertet werden [17]. Daher wurde ein Verfahren zur präzisen simultanen Bestimmung dieser Steroide in Serumproben entwickelt. Unter Verabreichung bilanzierter Kostformen sollte mit Hilfe dieser analytischen Methode der Einfluß von Nahrungscholesterin und -fettsäuren auf die Absorption und Biosynthese von Cholesterin beim Menschen bestimmt werden.