Developmental windows of vitamin D supplementation for optimal metabolic health

About This Grant

ABSTRACT: Obesity is prevalent among adults (>40%) and children (~20%) in the U.S. and is expected to increase dramatically in the next 25 years. Addressing the obesity epidemic is vital for public health because of its wide range of comorbidities including deadly conditions such as stroke, hypertension, diabetes, heart disease, liver disease, sleep apnea, pregnancy complications, and cancer. Most clinical interventions for obesity target individuals who are already obese. However, a growing body of research demonstrates that obesity can be caused by adverse events during development that drive irreversible effects on metabolic programming. This work highlights a critical need for preventative measures to address the obesity epidemic. Vitamin D is an essential nutrient that has recently been implicated in obesity. This has the potential to impact a large population since up to 80% of pregnant women are deficient in vitamin D (VDD) and emerging studies implicate this may disrupt developmental programming of metabolism and increase offspring susceptibility to obesity later in life. This proposal will leverage our novel mouse model of VDD-induced adiposity (a naturally genetically divergent Collaborative Cross (CC) mouse lineage) to model the human condition so we can better understand the developmental mechanisms driving obesity and target them for effective interventions. The mouse serves as a vital model for studying this important question not only because of its conserved vitamin D biology but also because mouse research allows us to avoid ethical limitations that inhibit studying VDD in human pregnancy and provides control over environmental and genetic confounders present in human populations. The proposed study aims to: (1) Determine the importance of vitamin D sufficiency during pre-, peri-, or post-conceptional windows of development in driving the accumulation of adiposity and risk of obesity-related comorbidities later in life; and (2) Define the developmental timing of VDD-induced transcriptional dysregulation and investigate its role in disruption of metabolic programming. Addressing these gaps in our understanding of the role of VDD in developmental mechanisms of obesity will help determine the relative importance of VitD monitoring and timely interventions for VDD during pregnancy to protect offspring metabolic health so that effective guidance can be developed.