Obesity Is a major public health problem worldwide and recent work has suggested that exposure to a suboptimal eariy environment may increase the risk of becoming obese. Epidemiological data show that an unfavorable intrauterine environment has long-term consequences in offspring including hypertension, cardiovascular disease, type 2 diabetes, obesity and neuropsychiatric disease. Specifically, prenatal stress and/or consumption of a high fat dieL characteristics of modern day human lifestyle, have been shown to lead to metabolic disorders such as obesity and Insulin resistance in offspring. However, the mechanisms involved are not well understood. The overall goal of this proposal is to characterize the short- and long-tenn effects of changes in the prenatal environment - stress and nutrition - on the behavioral and physiological development of offspring and to explore the possible neuropeptide and epigenetic mechanisms involved using a rat animal model.
Specific aims are: 1) To detemiine the developmental time course of behavioral and endocrine alterations resulting from prenatal stress. We will also test the hypothesis that prenatal stress will accentuate diet-induced obesity, Timepoints during lactation, adolescence, and adulthood will be examined to characterize the phenotype and to direct examination of possible mechanisms;2) To test the hypothesis that prenatal stress, high fat diet, or both result in alterations in neuropeptide systems regulating energy homeostasis that are consistent with other rodent models of obesity;and 3) To test the hypothesis that prenatal stress and nutrition results in obesity in offspring through epigenetic modifications via differential DNA methylation of genes that are critical to energy homeostasis. These experiments will enhance our understanding of the etiology of obesity and metabolic disease ultimately allowing the development of rational clinical interventions for such conditions.

Public Health Relevance

The prenatal environment plays a significant role in determining the health and well-being of offspring. This project will determine the effects of prenatal stress and maternal high fat diet on the metabolic phenotype of offspring. These studies will enable determination of the possible disease mechanisms involved in development of disease such as obesity and diabetes and provide information for establishment of more effective treatment ahd prevention strategies.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Grave, Gilman D
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Johns Hopkins University
Schools of Medicine
United States
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