Location: Diet, Genomics and Immunology Laboratory
Project Number: 8040-51530-058-03-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 1, 2017
End Date: Aug 30, 2022
Obesity-related chronic diseases such as diabetes and cardiovascular diseases (CVD) are serious health problems worldwide including the United States. Furthermore, 4 to 10% increase is expected annually in diabetes and CVD in the U.S. and worldwide. Modern sedentary life styles, lack of exercise, and/or unhealthy diets often with high calories have been mostly responsible for increasing obesity-induced diabetes and CVD. Although the cellular and molecular events related to obesity-induced diabetes and CVD are still being elucidated, subclinical inflammation has been considered a significant risk factor for the progression of diabetes and CVD. Interestingly, some food components have been believed to have positive effects on subclinical inflammation, diabetes, CVD and other diseases, but the mechanisms behind these foods and their components responsible for these actions remain to be elucidated. Therefore, in this proposal, we plan to assess differential responses in nutrient bioavailability and metabolic pathways in healthy, lean or obese individuals exposed to bioactive compounds in coffee, soy, rice, wheat, and other foods grown under specific conditions (objective 1) and to determine the differential responses to exposure based on genotype/phenotype characterization for specific metabolic pathways in healthy, lean or obese individuals (objective 2) in order to determine bio-efficacy of the proposed foods/components and define their mechanisms behind purported actions in humans at different nutritional status.
To accomplish the two objectives proposed in this study, human studies will be conducted in healthy volunteers who will consume controlled diets that vary in the content of specific foods, characterized by their fingerprint of bioactive compounds and reported to have effects on metabolic pathways implicated in obesity-related health outcomes such as insulin sensitivity, inflammation, cardiovascular, renal or hepatic dysfunction. Several biomarkers for obesity, subclinical inflammation, diabetes, and cardiovascular, renal or hepatic dysfunction will be selected and measured in order to determine bio-efficacy of foods and their bioactive components. Also, metabolites will be measured in blood and urine to determine potential metabolic pathways of food components in humans at different nutritional status. Furthermore, the expression of genes related to inflammatory pathways (including cytokines, chemokines) will be assessed by real time RT-PCR in peripheral white blood cells, and genomic variations in humans at different nutritional status will be determined by examining single-nucleotide polymorphism (SNPs).