Investigating the role of metabolic programming in vitamin D deficiency induced adiposity

点击翻译按钮获取中文摘要

ABSTRACT 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.