Project Number: 1950-51000-059-00
Project Type: Appropriated

Start Date: May 01, 2004
End Date: Apr 30, 2009

Objective:
LAB:Lipid Metabolism To determine the effect of altering dietary composition by restricting carbohydrates, fats, glycemic load, or total calories on body weight, and cardiovascular risk factors in overweight and obese subjects in the free-living state. To determine the effect of altering fat and carbohydrate level as well as carbohydrate type or glycemic index and load on weight loss and cardiovascular risk factors in overweight or obese subjects, under controlled, ad libitum, and isoweight conditions. To determine the effect of the standard 2005 Pyramid Diet versus a low glycemic load Pyramid Diet on weight loss and heart disease risk factors in overweight and obese subjects living in a free-living state. To develop and test an interactive web-based program to provide an optimal diet and exercise program for middle-aged and elderly subjects for weight and heart disease reduction. To observe the interactions of nutritional factors, especially intake of calories, types of fat, types of carbohydrate, level of physical activitiy, and different genetic factors on lipoprotein subspecies, obesity, metabolic sydrome, inflammatory markers, and heart disease risk in overweight and obese subjects with premature cardiovascular disease as compared to age and gender-matched control subjects within populations. To 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) Examine the efficacy of selectively bred and genetically modified vegetable oils and new sources of plant sterols on cardiovascular disease risk factors in middle-aged and older hypercholesterolemic female and male subjects. 2) Determine the effect of soy protein on cardiovascular risk factors in middle-aged and older hypercholesterolemic female and male subjects. 3) Determine the impact of diet and genotype on cholesterol homeostasis and cardiovascular health in the Framingham Offspring Study-Cycle 6. 4) Relate diet-induced changes in plasmalipid and lipoprotein levels to functional changes in gene expression and atherosclerotic lesion formation in Golden-Syrian hamsters.

Approach:
LAB: Lipid Metabolism Analyses of data in 160 overweight and obese subjects who were randomized to a one year program to test the efficacy of the Atkins (low carbohydrate), Ornish (low fat), Weight Watchers, (balanced caloric restriction) and Zone Diets (high protein, low glycemic index) in promoting weight loss and heart disease risk reduction. Complete studies in 80 overweight and obese people given controlled feeding studies in which calories were restricted by one third to determine whether fat restriction (15% versus 30%) or glycemic index (high versus low) of the carbohydrate had impact on weight loss, body composition, and heart disease risk factors (blood pressure, glucose, lipid levels, C reactive protein) other than through caloric restriction. Carry out controlled feeding and metabolic studies in 20 subjects comparing the effects of sucrose and starch isocalorically on plasma lipoprotein metabolism. Collect DNA samples on 1000 obese subjects and compare their genotypes at specific gene loci related to obesity versus an equal number of control subjects. Develop and test a web based diet and exercise program for weight loss and heart disease risk reduction in obese subjects (n=100). Carry out animal (rabbit) and cell studies (human hepatoma G2 cells) to examine the effects of different types of carbohydrates and fatty acids on the expressions of genes involved in lipid metabolism and inflammation. LAB:Cardiovascular Nutrition Diets will be developed that incorporate 20% of energy as the experimental fat (2/3 of the total fat content of the diet), with the balance of the macronutrients consistent with current recommnedations to maintain heart health. Human studies will likewise be carried out to assess the effect of foods derived from soybeans but varying in processing technique on measures of cardiovascular health in middle-aged and older hypercholesterolemic female and male subjects. Diets will be developed that incorporate 10% of energy as soybean derived protein. Using samples previously collected from the Framingham Offspring Study, the cardiovascular nutrition lab will quantify plasma concentrations of indicators of cholesterol homeostasis in study participants diagnosed with cardiovascular disease and/or >50% carotid stenosis and matched control subjects and integrate these data with the pertinent dietary, biochemical and genetic data available. Subsequent work will characterize the balance of plasma samples to established normal ranges for the indicators of cholesterol homeostasis. Lastly, in order to understand the underlying mechanisms by which diet alters plasma lipid and lipoprotein concentrations, hence heart disease risk, the Golden-Syrian hamster will be used as an animal model to relate diet-induced changes in plasma lipid and lipoprotein levels to functional changes in gene expression and atherosclerotic lesion formation.