Biochemical markers which accurately and objectively assess the dietary fat intake are necessary to investigate the connection between dietary fat and cancer. Dietary fat influences the concentrations of plasma lipoproteins. Traditionally, decreases in plasma total and low density lipoprotein (LDL) cholesterol are used to assess compliance. Recent data from our laboratory, obtained in women, suggest that changes in high density lipoproteins (HDL), especially HDL2 subfraction, provide more direct information about the dietary fat in short as well as long-term. The relationship between LDL and fat intake may be an indirect one, related to the changes in body weight and fat mass. A recent report also demonstrates that HDL is the best predictor of fat intake in women, whereas LDL is in men. The hypotheses of the Current Proposal are; 1. Changes in lipid concentration and particle size of HDL correlate with the changes in dietary fat, 2. Fatty acid composition of HDL reflects the quality of dietary fat, 3. Composition of HDL, ratios of lipid and protein to each other, reflects the amount of fat intake, independent of inter-individual variations in HDL concentrations. 4. Changes in HDL during short-term fat- restriction are similar to the changes in the long-term. Accordingly, the designated biomarkers of the study are; free-cholesterol, cholesteryl ester, triglyceride, phospholipid, apoprotein Al, particle size and fatty acid composition of HDL, including HDL2 and HDL3. Adipose-lipoprotein lipase and plasma cholesterol ester transfer protein are also designated markers, since they exchange lipids and apoproteins between HDL and other lipoproteins. The experimental design proposes studying 64 healthy, post-menopausal women. Each person is studied for 12 months; during a Controlled Low-Fat- Feeding (4-months) and a Self-Selected Low-Fat-Feeding (8-months) period. During the Controlled-Feeding, food is provided by the study. Dose response of HDL both to a decrease and an increase in fat-intake is tested by a step wise reduction from the baseline level to 25% and then to 15%, followed by a return to 25%. The time course is determined by blood tests at 2 and 4 weeks after each dietary change. The long-term reproducibility is tested during a Self-Selected 15%-fat diet, using commercially available food products for 8 months. The predictive value of the HDL is also compared with other markers; i.e. total and LDL-cholesterol, apoprotein B, fatty acid composition of platelets and plasma. Biometric measurements which can influence the response of biomarkers are also determined; i.e. weight, waist to hip ratio, body composition, resting energy expenditure. The proposed investigation will provide comprehensive information about the value of HDL as a marker of dietary fat intake in post-menopausal women.
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