Location: Jean Mayer Human Nutrition Research Center On Aging
Project Number: 8050-51000-103-000-D
Project Type: In-House Appropriated
Start Date: Apr 17, 2019
End Date: Mar 11, 2024
Objective:
Objective 1: Determine the effect of food components and their metabolites, dietary patterns, and lipid-modifying therapies on cardiometabolic risk factors and lipoprotein, sterol, bile acid, and fatty acid metabolism in humans, and using animal, and in vitro models.
Sub-objective 1.A: Elucidate the relationship between dietary patterns, with and without statin therapy, on atherosclerotic lesion development and concomitant tissue-specific inflammation using the Ossabaw pig as an experimental model.
Sub-objective 1.B: Compare the effects of an isocaloric exchange of simple-carbohydrate (carb), refined-carb, and unrefined-carb on (i) plasma cardiovascular risk factors, (ii) targeted metabolomic and lipidomic markers, and (iii) gut microbiome signatures in humans.
Objective 2: Identify novel biomarkers of food intake (e.g., metabolomic, lipidomic, proteomic, and microbiome) and relate them to cardiovascular health.
Sub-objective 2.A: Determine the differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation, relative to placebo, on (i) plasma measures of cardiovascular risk, and (ii) biomarkers of inflammation and inflammatory cell gene expression in subjects with elevated inflammatory status.
Sub-objective 2.B: Evaluate the effects of very long chain omega-3 ('-3) fatty acid supplementation (1.86 g EPA and 1.5 g DHA daily) on the composition and functionality of high density lipoprotein (HDL) subpopulations, and the influence thereof on coronary artery atherosclerotic plaque burden in individuals with stable coronary artery disease on statins.
Approach:
Cardiovascular disease continues to be the leading cause of death and disability in the United States. The risk of developing cardiovascular disease increases with age. Preventive measures, especially dietary modification, are more efficacious and cost effective than treatment. However, some dietary recommendations, particularly related to carbohydrate and fat type, are enmeshed in controversy. This controversy undermines public confidence in dietary guidance, thereby impeding efforts to improve the overall quality of the American diet. To address this conundrum, in the next 5 years, the Cardiovascular Nutrition Laboratory will determine the effect of food components and their metabolites, dietary patterns, and lipid-modifying therapies on cardiometabolic risk factors and lipoprotein, sterol, bile acid, and fatty acid metabolism in humans, and using animal and in vitro models. We will accomplish this by determining the effect of dietary modification on cardiovascular health by elucidating the relationships among diet, tissue specific inflammation and atherosclerosis progression using the Ossabaw pig model; investigating the effect of carbohydrate type on cardiovascular disease risk factors and the gut microbiome by conducting human intervention trials; and assessing the relationship among very long chain omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid), inflammation and coronary artery atherosclerotic plaque progression using in vitro and in vivo approaches. More specifically, we will elucidate the relationship between dietary patterns, with and without statin therapy, on atherosclerotic lesion development and concomitant tissue-specific inflammation in the Ossabaw pig, and compare the effects of an isocaloric exchange of simple-carbohydrate, refined-carbohydrate, and unrefined-carbohydrate on cardiovascular risk factors, targeted metabolomic and lipidomic markers, and gut microbiome signatures in humans. We will assess potential complementary and/or synergistic effects between dietary modification and pharmacotherapy intended to reduce cardiovascular disease risk. Additionally, the Cardiovascular Nutrition Laboratory will identify novel biomarkers of food intake (e.g., metabolomic, lipidomic, proteomic, and microbiome) and relate them to cardiovascular health by determining the differential effects of very long chain omega-3 acid supplementation on plasma measures of cardiovascular risk and biomarkers of inflammation and inflammatory cell gene expression in individuals with elevated inflammatory status, and evaluating the effects of very long chain omega-3 fatty acid supplementation on the composition and functionality of high density lipoprotein subpopulations, and the influence thereof on coronary artery atherosclerotic plaque burden in individuals with stable coronary artery disease treated with statins. We will use these data to better understand the relationship between diet and cardiovascular health. The results of the proposed work will help facilitate updating and refining the Dietary Guidelines for Americans intended to support healthy aging.
