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

研究代谢编程在维生素 D 缺乏引起的肥胖中的作用

基本信息

批准号：
10057754
负责人：
Folami Y Ideraabdullah
金额：
$ 18.92万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10057754
关键词：
Address Adipose tissue Adult Affect Aftercare Automobile Driving Citric Acid Cycle Clinical Research DNA Methylation Development Diagnosis Energy Metabolism Epigenetic Process Event Exhibits Expenditure Fatty acid glycerol esters Foundations Future Genes Genetic Gluconeogenesis Glycolysis Health Human Impairment Inbred Mouse Indirect Calorimetry Individual Insulin Resistance Intervention Lead Life Link Liver Metabolic Metabolic Diseases Metabolic dysfunction Metabolism Micronutrients Mitochondria Obesity Outcome Phenotype Play Population Predisposition Pregnancy Preventive measure Production Public Health Publishing Pyruvate Research Research Design Resistance Respiration Risk Rodent Model Role Study models Susceptibility Gene Testing Translating Treatment Efficacy United States Vitamin D Vitamin D Deficiency Work adult obesity carbohydrate metabolism cell type early detection biomarkers effective intervention efficacy testing epidemiology study fat burning fatty acid oxidation genome-wide glucose metabolism improved innovation lipid metabolism lipid transport metabolome mouse model novel obesity in children offspring prevent response restoration sperm cell

项目摘要

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.

抽象的怀孕期间缺乏维生素 D 的情况很普遍（在美国流行病学研究中这一比例高达 91%）。啮齿动物模型表明，发育过程中维生素 D 缺乏 (DVD) 会导致最新研究表明，尽管肥胖和代谢功能障碍，这些影响仍会持续到成年期。恢复维生素 D 充足性这涉及发育编程，这是一种机制。由于表型的稳定“编程”，发育过程中的负面事件会导致持续的影响在这里，我们建议以我们实验室的新发现为基础，即基因不同的个体存在差异。我们将解决有关 DVD 的持续影响的三个重要问题。 DVD 在肥胖发展规划中的作用：(1) DVD 会扰乱哪些代谢过程改变肥胖？；（2）DNA甲基化失调是DVD效应持续存在的机制吗？成年期？；（3）哪些基因和/或表突变导致易感性差异。研究结果将为改善 DVD-D 的诊断和干预提供至关重要的机制证据此外，这项研究将有助于识别易感性。这些因素可能会作为预防性长期结果的有价值的早期检测生物标志物措施、测试治疗效果的目标以及改进研究设计的驱动因素，以转化我们的研究成果对人类的研究结果。