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United States Department of Agriculture

Agricultural Research Service

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Location: Jean Mayer Human Nutrition Research Center On Aging

2011 Annual Report

1a. Objectives (from AD-416)
LAB: LIPID METABOLISM 1. To determine the effect of altering dietary composition by restricting carbohydrates, fats, glycemic load, or total calories on plasma lipoproteins, blood pressure, glucose homeostasis, and body weight, cardiovascular risk factors in overweight and obese subjects under controlled feeding conditions and in the free-living state. 2. Develop and test an interactive program to provide an optimal diet and exercise program for middle-aged and elderly overweight and obese subjects for weight loss and heart disease reduction. 3. Observe the interactions of nutritional factors, especially intake of calories, types of fat, types of carbohydrate, level of physical activity, and different genetic factors on lipoprotein subspecies, obesity, metabolic syndrome, inflammatory markers, and heart disease risk in overweight and obese subjects and subjects with premature cardiovascular disease as compared to age- and gender-matched control subjects within populations. 4. Determine the in vitro and in vivo effects of dietary fatty acids, cholesterol, carbohydrates, hormone levels, hormonal replacement, B vitamins, cholesterol biosynthesis inhibition and cholesteryl ester transfer protein inhibition on lipoprotein metabolism and gene expression, and inflammation in human liver cells (HepG2) and in human subjects under metabolic ward conditions using stable isotopes. LAB: CARDIOVASCULAR NUTRITION 1. Assess the relationship between plasma biomarkers of nutrient intake and heart health. 2. Characterize the relationship between plasma markers of cholesterol homeostasis, dietary intake and intestinal cholesterol absorption protein genotypes, and heart health using samples from the Framingham Offspring Study. 3. Assess the value of glycemic index (GI) as a component of dietary guidance to promote heart health and decrease the risk of chronic diseases associated with aging. 4. Assess the relationship between the red blood cell fatty acid profiles and indicators of heart health in subjects consuming diets enriched in trans fatty acids derived from ruminant fat and partially-hydrogenated vegetable oils. 5. Assess the efficacy of a comprehensive family centered lifestyle modification program – Family Weight Study (FamWtStudy) – using biomarkers of nutrient intake and cardiovascular risk factors in family member pairs (female parent/guardian and child) after initiation of a comprehensive year long program.

1b. Approach (from AD-416)
LAB: LIPID METABOLISM In the next 5 years the Lipid Metabolism Laboratory will continue to test optimal lifestyle strategies for the prevention of coronary heart disease (CHD). Human intervention studies will assess effects of supplementation with omega 3 fatty acids and plant sterols versus placebo on CHD risk factors, caloric restriction in older overweight subjects using diet either low or high in glycemic load on CHD risk factors, and an aggressive lifestyle and omega 3 fatty acid supplementation program in overweight subjects with CHD versus usual care on CHD risk factors, cognitive function, and change in coronary atheroma. Population studies will examine the interaction of diet as assessed by questionnaires, genetics as assessed by genotyping, and biochemical markers of insulin resistance, inflammation, and alterations in lipoprotein particles on CHD risk and cognitive decline in participants in the Framingham Heart Study (original cohort and offspring). Human metabolic studies will examine the effects of diets low in animal fat and cholesterol with or without fish versus average American diets on lipoprotein metabolism. We will also examine the effects of estrogens and niacin on human plasma lipoprotein metabolism. Cell studies will examine the mechanisms of action of different fatty acids on the expression of specific genes involved in reverse cholesterol transport in human liver cells and in macrophages. Our overall objectives are to develop optimal lifestyle strategies for the prevention of CHD. LAB: CARDIOVASCULAR NUTRITION In the next 5 years the Cardiovascular Nutrition Laboratory will assess the relationship between cardiovascular health and biomarkers of nutrient intake relative to food frequency data using Women’s Health Initiative samples by measuring nutrient intake biomarkers (plasma phospholipid trans fatty acids, eicosapentaenoic acid and docosahexaenoic acid, and phylloquinone and dihydrophylloquinone) and relating these data to cardiovascular health; identifying dietary patterns from food frequency questionnaire data and relating to cardiovascular health; and developing an algorithm using these data that best predicates cardiovascular health; assess the relationship between biomarkers of cholesterol homeostasis and modifiers thereof using plasma samples from the Framingham Offspring Study by measuring plasma cholesterol absorption (sitosterol, campesterol, cholestanol) and biosynthesis (desmosterol, lathosterol, squalene) marker concentrations and relating these data to cardiovascular health as modified by dietary intake and selected genotypes; and evaluate glycemic index (GI) as a component of dietary guidance to decrease chronic diseases risk by determining the reproducibility and variability of GI value determinations in volunteers differing in BMI, age, and gender; assessing the effect of macronutrient amounts and combinations, and fiber on GI and glycemic load (GL) value determinations; and determining the effect of macronutrient composition (carbohydrate, fat, and protein) of a prior meal (“second meal” effect) on GI and GL value determinations.

3. Progress Report
This progress report includes the work of two subordinate projects at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress reports, see 1950-51000-072-01S (Lipoproteins and Nutrition) and 1950-51000-072-02S (Diet and Biomarkers of Cardiovascular Health).

4. Accomplishments

Review Publications
Matthan, N.R., Ip, B., Resteghini, N., Ausman, L., Lichtenstein, A.H. 2010. Long-term fatty acid stability in human serum cholesteryl ester, triglyceride, and phospholipid fractions. Journal of Lipid Research. 51:2826-2832.

Corcoran, M.P., Meydani, M., Lichtenstein, A.H., Schaefer, E.J., Dillard Hirschel, A., Lamon-Fava, S. 2010. Sex hormone modulation of proinflammatory cytokine and CRP expression in macrophages from older men and postmenopausal women. Journal of Endocrinology. 206(2):217-224.

Chung, M., Balk, E.M., Ip, S., Lee, J., Terasawa, T., Raman, G., Trikalinos, T., Lichtenstein, A.H., Lau, J. 2010. Systematic review to support the development of nutrient reference intake values: challenges and solutions. American Journal of Clinical Nutrition. 92(2):273-276.

Tybor, D., Lichtenstein, A., Dallal, G., Daniels, S., Must, A. 2011. Independent effects of age-related changes in waist circumference and BMI z scores in predicting cardiovascular disease risk factors in a prospective cohort of adolescent females. American Journal of Clinical Nutrition. 93:392-401. PMID 21147855.

Kuang, Y., Paulson, K., Lichtenstein, A., Matthan, N., Lamon-Fava, S. 2011. Docosahexaenoic acid suppresses apolipoprotein A-I gene expression through hepatocyte nuclear factor-3beta. American Journal of Clinical Nutrition. 94:1-8.

Corcoran, M., Lichtenstein, A., Meydani, M., Dillard, A., Schaefer, E., Lamon-Fava, S. 2011. The effect of 17 beta-estradiol on cholesterol in human macrophages is influenced by the lipoprotein milieu. Journal of Molecular Endocrinology. 47(1):109-117.

Lamon-Fava, S., Asztalos, B.F., Howard, T., Reboussin, D.M., Horvath, K., Schaefer, E.J., Herrington, D.M. 2010. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women. Clinical Endocrinology. 72(2):169-75.

Schaefer, E. 2010. Northern light: a commentary on the 2009 Canadian Guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in adults. Clinical Chemistry. 56(4):502-504.

Ai, M., Otokozawa, S., Asztalos, B.F., Ito, Y., Nakajima, K., White, C.C., Cupples, A.L., Wilson, P.W., Schaefer, E. 2010. Small dense low density lipoprotein cholesterol and coronary heart disease: results from the Framingham Offspring Study. Clinical Chemistry. 56(6):1-10.

Lichtenstein, A. 2011. Dietary effects on cardiovcascular risk factors. In: Grundy, S., editor. 5th Edition. Philadelphia, PA: Current Medicine, Inc.

Lichtenstein, A. 2010. Health claims and dietary guidance to reduced cardiovascular disease risk in the United States. In: Salminen, S., Kniefel, W., Ouwehand, A., editors. Lactic Acid Bacteria. New York, NY: Marcel Dekker, Inc.

Lichtenstein, A. 2010. Nutrition and CVD risk. In: Eckel, R., editor. Metabolic Risk for Cardiovascular Disease. Oxford, UK: Wiley-Blackwell.

Dillard, A., Matthan, N., Lichtenstein, A. 2010. Appropriateness of the hamster as a model to study diet-induced atherosclerosis. Nutrition Metabolism and Cardiovascular Disease. 10:89. PMID 21143982.

Asztalos, B., Tani, M., Schaefer, E. 2011. Metabolic and functional relevance of HDL subspecies. Current Opinion in Lipidology. 22(3):176-185.

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