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Influence of diet fat saturation on rates of cholesterol synthesis and esterification in healthy young men Mazier, Marie Jeanne Patricia


To examine the effect of diet fat type on rates of cholesterol synthesis and esterification during feeding and fasting, nine healthy male subjects were fed solid-food diets of 40% fat as predominantly either olive oil (MONO), safflower-oil margarine (POLY), or butter (SAT). At the end of each two-week diet trial, subjects were given deuterium (D) oxide orally and de novo synthesis was measured from D incorporation into cholesterol and interpreted as rates of fractional synthesis (FSR) (pools/day) into the rapidly exchangeable free cholesterol (FC) pool. Absolute synthesis rates (ASR) were calculated as the product of FSR and the FC pool. Pool size for each subject was obtained from analysis of the specific activity decay curve of an intravenous injection of 4-14C-cholesterol over nine months. Synthesis was measured over two consecutive 12-h fed periods followed by two consecutive 12-h fasted periods. Serum samples were also assayed for lathosterol concentration, an index of cholesterol synthesis. Serum cholesterol and non-HDL cholesterol concentrations were highest on the SAT diet, lowest (P<0.001) on the POLY diet and intermediate on the MONO diet, triglyceride levels were greater (P<0.03) on the SAT diet than on the POLY diet, and HDL levels were lowest (P<0.05) on the SAT diet and highest on the MONO diet. Cholesterol D enrichment and FSR during each 12-h period were greater (P<0.014) on the POLY diet than on the SAT diet; MONO enrichment and FSR were not significantly different from those on the other two diets. Similar results were obtained for rates of cholesterol esterification (P<0.001). Deuterium enrichment data suggested, and lathosterol data confirmed, that free cholesterol synthesis was greater during the fed period than during the fasted period (P<0.01); however, this could not be confirmed for rates of cholesterol esterification. Results suggest that POLY fat feeding augments de novo cholesterol synthesis without adverse effects on total serum cholesterol concentrations, and that the deleterious effects of SAT fat on serum cholesterol are not brought about by augmented de novo synthesis. Finally, the combination of deuterium incorporation and mathematical modelling produces estimates of daily cholesterol synthesis which are compatible with those invoked by more laborious techniques.

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