This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The incidence of preventable metabolic diseases in children has increased markedly over the past 2 decades. Currently, there is little information to determine the underlying causes or whether therapeutic or dietary interventions might be successful at preventing or reducing metabolic health risks in children from obese pregnancy. These studies use a nonhuman primate (NHP) model to investigate the impact of poor maternal metabolic health and diet on the development of metabolic systems in the developing fetus, as well as its postpartum growth, development, and susceptibility to diet induced obesity and diabetes. For these studies, breeding NHPs are chronically maintained on a diet high in fats and calories (HFD). This proposal focuses on the placenta, pancreas, liver and muscle that are critical for normal regulation of body weight and glucose homeostasis. The hypothesis is that abnormalities beginning with placental dysfunction directly contribute to life-long risk for metabolic disease. Furthermore, it is hypothesized that supplementation with agents that reduce oxidative stress and inflammation will prevent or attenuate the structural, metabolic, and molecular disturbances observed during pregnancy while on a HFD. We are also determining if dietary supplements with either fish oil or resveratrol, to prevent inflammation, oxidative stress, will provide similar protection. These studies will identify the risks and complications in the developing fetus associated with poor maternal metabolic health and diet. Furthermore, these studies will test dietary supplements/interventions that can be quickly translated to the clinic that may help prevent or reduce metabolic diseases in children.
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