The purpose of this research is to examine the effects of diets high in certain fatty acids and bioactive molecules (pistachio nuts, peanuts, walnuts, fish oil, lean beef for example) to evaluate their effects on multiple cardiovascular disease (CVD) risk factors. These risk factors include lipids and lipoproteins, apolipoproteins, oxidation, inflammation, insulin, glucose, blood pressure, endothelial health, and genetic expression of various genes. We propose that increasing the dietary intact of ω3-PUFAs in the context of a healthy diet, will improve CVD risk factors. These hypothesis are tested using cell culture and molecular biology techniques as well as clinical trials.
Example 1. Molecular Nutrition
For examination of each of the potential beneficial dietary component we will : (1) Examine the anti-inflammatory effects of oil, ethanol and water soluble extracts from the dietary component being studied concurrently in the clinic. The hypothesis being tested is that bioactives and polyunsaturated fatty acids in the nut will exert anti-inflammatory effects directly on the macrophages. This will be evaluated by gene expression and through the release of cytokines into the media; (2) Determine the mechanism by which oil, ethanol and water soluble extracts from these dietary components exert their beneficial effects. The hypothesis being tested is that resveratrol and other polyphenols found in the many nuts and polyunsaturated fatty acids in the nut will exert anti-inflammatory effects via nuclear receptors such as PPAR. Sensitive reporter assays as well as gene expression studies will be used to evaluate the mechanism of action of bioactives within the food; (3) Establish novel “biomarkers” to be utilized in subsequent clinical studies on the dietary component. Our hypothesis for these studies is that more sensitive, predictive and specific biomarkers of peanuts products can be determined by gene expression microarrays.
Example 2. Clinical Nutrition
The design of diets to impact circulating levels on ω3-PUFAs and anti-inflammatory bioactive molecules will be performed by collaborators at Penn State University. Following this intervention, established and emerging CVD risk factors including lipids and lipoproteins, apolipoproteins, antioxidant activity, inflammatory cytokines, and cellular adhesion molecules, insulin, glucose, blood pressure, endothelial health (FMD) will be examined. It is at this point that the molecular nutrition research described above will be utilized. (1). The specific biomarkers identified using altered gene expression will be utilized. Lymphocytes will be extracted from individuals at the end of the intervention period. Quantitative gene expression studies will determine if the same genetic alterations seen by direct addition of the nutritional component or bioactive is observed in vivo. Often the gene expression studies using real-time PCR are much more sensitive that the established CVD risk factors mentioned above (2). The mechanism of action of a nutritional component or bioactive can be used to determine why certain individuals are not as responsive as others. Many of the nuclear receptors examined as being targets of dietary lipids are polymorphic in humans. Using sensitive PCR techniques we will examine know single nucleotide polymorphisms (SNPs) in the targets for the dietary component.