MATERNAL DIET MODIFIES THE FETAL PRIMATE EPIGENOME AND CIRCADIAN GENE EXPRESSION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. According to the Barker's Fetal Origins of Adult Disease Hypothesis, perturbations in the gestational milieu influence the development of adult diseases. This occurs through the reprogramming of gene expression via epigenetic changes in chromatin structure. It is clear from studies done in rodents that numerous maternal manipulations can cause epigenetic modifications in the developing fetus that results in long-term modification of body weight homeostasis. Surprisingly, there has been a lack of study of whether modification of maternal dietary fat can cause similar epigenetic modifications in the fetal offspring. Furthermore, there has been no evidence of whether epigenetic modifications occur in primate species. The general hypothesis of this proposal is that diet and metabolic health during pregnancy and the early neonatal period significantly contribute to the development of metabolic diseases in children. This proposal focuses upon the effects of a maternal high fat diet upon the fetal and postnatal epigenetic characteristics of circadian genes in the liver and hypothalamus of the NHP. For these studies liver and hypothalamic are obtained samples from offspring of animals maintained either on a control diet or a high fat diet. Changes in chromatin structure, histone modifications (histone acetylation/methylation) as well as changes in expression of genes that are epigenetically modified will be characterized. A special focus of these studies is to characterize changes in circadian regulation of energy homeostasis. These studies will provide critical insight into the underlying mechanism by which maternal nutritional manipulations can cause long-term risks of metabolic diseases in offspring.