Project Number: 8050-51000-090-00-D
Project Type: In-House Appropriated
Start Date: Oct 1, 2014
End Date: Sep 30, 2019
LAB NAME: Nutritional Immunology 1: Determine the impact and underlying mechanisms of obesity during pregnancy on newborn's life-long immune and inflammatory responses and resistance to infectious diseases in appropriate animal models. 1A. To investigate the impact of maternal obesity on immune function and influenza infection in young offspring. 1B. To determine the role of inflammatory, oxidative stress, and selected epigenetic markers that are critical for immune response to influenza and the higher susceptibility of obese mothers’ offspring to influenza infection. 1C. To determine the impact of maternal obesity on immune function and resistance to infection through the life cycle. 2: Determine the effect and mechanisms of food components such as fruits and vegetables or whole grains influence on, and their interaction with, age on immune and inflammatory responses and related diseases in both animal models and human studies. 2A: To determine the impact of increased consumption of F&V on prevention of key age-related biologic dysfunctions and pathologies in a suitable animal model. 2B: To determine the effect of consumption of an isocaloric diet rich in whole grains (WG)[compared to refined grains (RG)] on gut microbiota, and immune and inflammatory responses. 3: Determine the effect of novel forms of iron on systemic and gut immune function, inflammation, oxidative stress. LAB NAME: Vascular Biology 1: Determine the effectiveness and underlying mechanisms of fruits/vegetables and Mediterranean style diets or their specific bioactive components in the prevention of atherosclerosis and survival using animal models of humans. 1A: Determine the effectiveness and underlying mechanisms of increased consumption F&V diets on prevention of atherosclerosis and survival using appropriate animal model of human atherosclerosis. 1B: Determine the effectiveness of natural bioactive polyphenols of foods and spices and their underlying mechanisms on prevention of atherosclerosis using appropriate animal models of human atherosclerosis. 2: Determine the efficacy of fruits/vegetables, avenanthramides from oats, and selected other bioactive compounds on alteration of microbiome and anti-microbial peptides, suppression of chronic inflammation of the GI tract, prevention of colon cancer and atherosclerosis in appropriate animal models. Under this objective, we will pursue the following sub-objectives: 2A: Determine the efficacy of bioactive phosphorylated tocopherols ('Tp) versus tocopherols on age-dependent decline of angiogenesis and suppression of atherosclerosis in vivo and ex-vivo. 2B: To determine the molecular signaling mechanisms by which 'TP induces angiogenesis. 3: Determine the effect of eight weeks consumption of an isocaloric diet enriched with whole grains (compared to refined grains) on gut microbiota, inflammatory and other risk predictors of atherosclerosis.
NUTRITIONAL IMMUNOLOGY: Aging is associated with dysregulation of immune and inflammatory responses, which contribute to several age-related diseases. Nutritional status including that during early life has been linked to health status of older adults, & nutritional interventions during different life stages including those during pregnancy are reported to have long-lasting effects on the health status of newborns. Long-term goal is to determine the underlying mechanisms of age-related immune & inflammatory dysregulation in order to develop nutritional interventions, which will prevent/reduce these alterations.  will determine the impact & underlying mechanisms of obesity during pregnancy on newborn's life-long immune & inflammatory responses & resistance to infectious diseases. To achieve this, we will use a diet-induced obesity mouse model and determine: 1) effect of maternal obesity on immune function and influenza infection in young offspring, 2) role of inflammatory, oxidative stress, and selected epigenetic markers in altered immune function and susceptibility to infection in offspring born to obese mothers, and 3) impact of maternal obesity on immune function and resistance to infection through the life cycle.  will determine the effect and mechanisms of food components such as fruits and vegetables or whole grains influence on, and their interaction with, age on immune and inflammatory responses and related diseases in both animal models and human studies. [2A], we will use a mouse model to determine whether the dietary supplementation with a variety of fruits and vegetables would impact health- and life-span through modulating oxidative stress, inflammation and the regulatory lipid, ceramide. [2B], we will conduct a dietary intervention trial in healthy middle-aged human participants to determine the effect of consumption of an isocaloric diet rich in whole grains compared to refined grains on gut microbiota, and immune and inflammatory responses. These studies will help develop effective strategies to improve health- and life-span of the aged through optimization of immune and inflammatory responses. VASCULAR BIOLOGY: Determine survival rates, prevention of atherosclerosis, and underlying mechanism(s) in LDLr-/- young to old mice using freeze-dried fruits, vegetables and cereal grains in a high fat diet. Further, we will use C57/BL and LDLr-/- mice to determine the causal relationship & underlying mechanism(s) of specific bioactive food components (such as curcumin, resveratrol, avenanthramides, and their combinations) on inhibition of dyslipidemia, fatty liver, inflammation, metabolic disorders, & atherosclerosis resulting from consuming a diet high in fat and/or sweeteners like sucrose & high fructose corn syrup. We plan to establish the causal relationship of increased consumption of whole grains versus refined grains and their capacity to improve oxidative & antioxidant status as well as surrogate markers of cardiovascular disease. We will investigate potential molecular mechanisms by which alpha-Tocopheryl phosphate (alpha-TP), a natural derivative of alpha-T, induces angiogenesis in vitro & in an in vivo animal model.