Vitamin D deficiency during pregnancy is prevalent (up to 91% in the United States). Epidemiological studies and rodent models demonstrate that vitamin D deficiency during development (DVD) leads to increased adiposity and metabolic dysfunction. Emerging studies show these effects can persist into adulthood despite restoration of vitamin D sufficiency. This implicates developmental programming, a mechanism by which negative events during development cause effects that persist due to stable ?programming? of phenotypic responses. Here, we propose to build on novel findings from our lab that genetically divergent individuals differ in susceptibility to the persistent effects of DVD. We will address three important questions regarding the role of DVD in developmental programming of adiposity: (1) Which metabolic processes are perturbed by DVD to alter adiposity?; (2) Is dysregulation of DNA methylation a mechanism of persistence of DVD effects into adulthood?; and (3) Which genes and/or epimutations are responsible for differences in susceptibility. These findings will provide mechanistic evidence that is critical for improving diagnoses and interventions of DVD- induced obesity and related effects. Furthermore, this study will facilitate the identification of susceptibility factors that will likely serve as valuable early detection biomarkers of long-term outcomes for preventative measures, targets for testing efficacy of treatments, and drivers of improved study design in translating our findings to human populations.
Vitamin D deficiency during pregnancy is a prevalent public health concern that increases offspring risk of metabolic disorders such as obesity and insulin resistance later in life. This study will use mouse models to characterize mechanisms responsible and identify differences in susceptibility between genetically diverse individuals. Findings will lay the foundation for future studies to test effects in human populations and improve our ability to diagnose, prevent and treat effects for optimal metabolic health across all populations.
