We propose an integrated series of clinical and biochemical investigations to better delineate the effects of specific dietary lipids on lipid and lipoprotein metabolism in human subjects. The influence of diets in which monounsaturated fatty acids represent the main source of fat will be investigated in terms of their lipid lowering effects compared to similar diets containing 30% of calories from omega-6 polyunsaturated fatty acids or primarily saturated fatty acids and both of these compared to a low fat diet. All diets will be fed to subjects with primary hypercholesterolemia and parameters of lipoprotein metabolism to be studied will include 125I-LDL turnover, cholesterol homeostasis assessed by serum and urinary excretion of mevalonic acid and cholesterol synthesis in freshly isolated mononuclear leukocytes. These four diets will be fed to subjects consuming a cholesterol-free diet and in the presence of 600 mg/day of dietary cholesterol. The metabolic effects of long chain polyunsaturated fatty acids derived from fish oil will be examined in studies outlined in Project 2. These studies aim to examine whether the hypotriglyceridemic effects of long-chain omega-3 polyunsaturated fatty acids are due primarily to eicosapentaenoic acid or docosahexaenoic acid by determining if these purified fatty acids (as dietary constituents) prevent carbohydrate induced hypertriglyceridemia. The mechanisms responsible for the reduction of HDL concentrations in hypercholesterolemic subjects fed a low cholesterol fish oil will be examined by performing kinetic studies with 125I-labeled HDL. The influence of fish oils on prostanoid formation will be examined in collaborative studies. These studies should further our knowledge concerning the anti-atherosclerotic effects of long chain omega-3 fatty acids. The influence of sterols on plasma lipid and lipoprotein concentrations will be examined in normal and hypercholesterolemic subjects fed diets supplemented with seafood sterols. Finally, the fourth project aims to examine the hypocholesterolemic effects of three phases of a prudent diet in volunteer subjects, establish a recipe development laboratory, and prospectively assess the effectiveness of dietary counseling as an adjunct to long-term control of plasma lipids in an outpatient setting. Overall, these studies should enhance our knowledge concerning the clinical and metabolic effects of specific dietary lipids and have direct therapeutic application to treatment of subjects with hypercholesterolemia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037940-05
Application #
3353895
Study Section
Special Emphasis Panel (SRC (08))
Project Start
1986-09-30
Project End
1992-11-30
Budget Start
1990-12-15
Budget End
1992-11-30
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Nordoy, A; Hatcher, L; Goodnight, S et al. (1994) Effects of dietary fat content, saturated fatty acids, and fish oil on eicosanoid production and hemostatic parameters in normal men. J Lab Clin Med 123:914-20
Anderson, G J; Tso, P S; Connor, W E (1994) Incorporation of chylomicron fatty acids into the developing rat brain. J Clin Invest 93:2764-7
Anderson, G J; Connor, W E (1994) Accretion of n-3 fatty acids in the brain and retina of chicks fed a low-linolenic acid diet supplemented with docosahexaenoic acid. Am J Clin Nutr 59:1338-46
Artaud-Wild, S M; Connor, S L; Sexton, G et al. (1993) Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox. Circulation 88:2771-9
Connor, W E; Connor, S L (1993) Importance of diet in the treatment of familial hypercholesterolemia. Am J Cardiol 72:42D-53D
Nordoy, A; Hatcher, L F; Ullmann, D L et al. (1993) Individual effects of dietary saturated fatty acids and fish oil on plasma lipids and lipoproteins in normal men. Am J Clin Nutr 57:634-9
Connor, W E; Prince, M J; Ullmann, D et al. (1993) The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control. Ann N Y Acad Sci 683:337-40
Greer, M A; Hagemenas, F C; Illingworth, D R (1992) Osmotic cell swelling stimulates receptor-mediated low density lipoprotein endocytosis and degradation. Horm Metab Res 24:454
Connor, S L; Gustafson, J R; Sexton, G et al. (1992) The Diet Habit Survey: a new method of dietary assessment that relates to plasma cholesterol changes. J Am Diet Assoc 92:41-7
Anderson, G J; Van Winkle, S; Connor, W E (1992) Reversibility of the effects of dietary fish oil on the fatty acid composition of the brain and retina of growing chicks. Biochim Biophys Acta 1126:237-46

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