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The overall goal of the project is to elucidate the molecular and cellular mechanisms that respond to selected health promoting food components to reduce the risk of chronic diseases such as cancers and obesity. A secondary aim is to explore the utility of a porcine model to test the effect of health maintenance via diet and identify resulting biomarkers that reflect health status.<P> Objective 1. Elucidate biological activities of health promoting phytochemicals from grape, soy, and cruciferous vegetables against development of breast and prostate cancer. <P>Objective 2. Identify molecular targets and mechanisms of action of health promoting food components in animal or in vitro models of cancer and obesity. <P>Objective 3. Ascertain the effects of specific probiotic strains in appropriate animal models of obesity. <P>Objective 4. Identify plant polyphenols and probiotics that affect adipocyte numbers, size, and fat accumulation, and the regulation of proinflammatory mRNA stability by tristetraprolin. <P>Objective 5. Tie together obesity, inflammation, and cancer mechanistically in appropriate animal or in vitro models.
Approach: Studies will evaluate if phytoalexins structurally similar to resveratrol exerts similar anti-prostate cancer effects; if soy phytoalexin glyceollins exert anti-prostate cancer effects; if phytochemicals modulate LXR-mediated pathways in prostate epithelial cells and modulate LXR-mediated pathways in macrophage. Other studies will determine if probiotic bacterial strains differ in their protective effects against chronic diseases related to obesity; regulate adipocyte numbers, size, and fat accumulation associated with the anti-inflammatory protein tristetraprolin (TTP); if obesity alters the macrophage phenotype and function in adipose tissue, colon, breast, and prostate following increased localized inflammation; and if broccoli-derived phytochemicals modulate LXR-responsive pathways in vivo. The studies will involve in vitro cell culture approaches confirmed by rodent and pig animal models.