Perinatal Exposure to Environmental DDT and Risk of Metabolic Syndrome

围产期接触环境滴滴涕和代谢综合征的风险

• 批准号: 8573076
• 负责人: Michele A La Merrill
• 金额: $ 24.86万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8573076
• 关键词: Address; Adipose tissue; Adult; Affect; Age; Aging; Animal Experimentation; Aromatic Hydrocarbons; Biological Markers; Birth; Blood; Blood Pressure; Body Burden; Body measure procedure; California; Child Development; Child health care; Cholesterol; Cohort Studies; DNA; Data; Daughter; Development; Diabetes Mellitus; Dilution Techniques; Dose; Endocannabinoids; Endocrine; Endocrinology; Environmental Epidemiology; Environmental Health; Epidemiologic Studies; Epidemiology; Etiology; Euglycemic Clamping; Exposure to; Fatty Acids; Foundations; Functional disorder; Glucose; Glucose Clamp; Goals; Gold; Homeostasis; Hormones; Human; Human Development; Hyperlipidemia; Hypertension; Insulin; Intramuscular; K-Series Research Career Programs; Laboratories; Lead; Learning; Life; Life Cycle Stages; Lipids; Lipolysis; Malaria; Measures; Medical; Mentors; Metabolic; Metabolic syndrome; Metabolism; Methodology; Methylation; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Participant; Pathway interactions; Perinatal; Perinatal Epidemiology; Perinatal Exposure; Persons; Phase; Phenotype; Physiological; Physiology; Population; Preparation; Prevalence; Prevention strategy; Relative (related person); Research; Research Training; Risk; Rodent; Role; Scientific Advances and Accomplishments; Scientist; Series; Signal Pathway; Signal Transduction; Staging; Techniques; Testing; Third Pregnancy Trimester; Tissues; Toxic Environmental Substances; Toxic effect; Toxicology; Tracer; Training; Training Programs; Triglycerides; Woman; Work; analytical method; blood glucose regulation; career; career development; cohort; design; developmental toxicology; diabetes risk; dichlorodiphenyltrichloroethane; endoplasmic reticulum stress; environmental chemical; epigenomics; experience; follow-up; genome-wide; glucose tolerance; in vivo; intrahepatic; lipid biosynthesis; lipid metabolism; middle age; organochlorine pesticide; post-doctoral training; programs; promoter; research study; response; trend; uptake

Project Summary The candidate seeks career development support that will build on her interdisciplinary training in toxicology and environmental epidemiology and enable her to advance her scientific career by investigating the possible contribution of DDT exposure in early life to risk of the metabolic syndrome and diabetes. The scientific goal is to test the hypothesis that perinatal exposure to DDT increases risk of metabolic syndrome in aging adults in a dose-dependent manner. The candidate proposes an integrated series of toxicologic and epidemiologic studies. The toxicologic studies (K99 MENTORED PHASE) will incorporate dynamic in vivo physiologic techniques such as metabolic tracers and euglycemic clamping developed in medical endocrinology to explore tissue specific mechanisms of perinatal DDT toxicity in mice. The independent (R00 PHASE) will involve follow-up of the now middle-aged daughters of women who participated in the Child Health and Development Studies birth cohort study in California over 40 years ago and will involve inter-generational life course analyses. The independent phase will conclude with research seeking to identify biomarkers of DDT metabolic toxicity in mice. Metabolic syndrome, often associated with obesity and diabetes, affects over 47 million US residents. Prevalence has increased rapidly in the past decade. The possibility of a toxic environmental chemical contribution to this upward trend is relatively unexplored. There are however, human and mechanistic laboratory data suggesting that organochlorine pesticides, DDT among them, are associated with increased risk of diabetes and the metabolic syndrome. DDT was used extensively in the US until 1972 and is still much used worldwide in malaria control. At the conclusion of training, the candidate will transition to an independent career focused on elucidation of the mechanisms of perinatal exposures involved in metabolic and endocrine dysfunction. These studies should lead to a better understanding of the possible role of environmental toxicants in the etiology of metabolic syndrome and diabetes and will establish a strongly interdisciplinary foundation for the candidate's future research.

项目摘要 候选人寻求职业发展支持，这将基于她的跨学科培训 在毒理学和环境流行病学上，使她能够发展自己的科学生涯 通过调查DDT暴露在早期生命中可能贡献的代谢风险 综合征和糖尿病。科学目标是检验围产期暴露的假设 DDT以剂量依赖性的方式增加了成年衰老成人代谢综合征的风险。这 候选人提出了一系列综合的毒理学和流行病学研究。这 毒理学研究（K99指导阶段）将在体内融合动态生理学 在医学中开发的代谢示踪剂和尤利科血糖夹等技术 内分泌学探索小鼠围产期DDT毒性的组织特异性机制。这 独立（R00阶段）将涉及对现在中年女儿的跟进 他参加了加利福尼亚州的儿童健康与发展研究出生队列研究 40多年前，将涉及世代间的生活课程分析。独立 阶段将在寻求识别DDT代谢毒性的生物标志物的研究中得出结论 老鼠。代谢综合征通常与肥胖和糖尿病有关，影响超过4700万 美国居民。在过去的十年中，患病率迅速增加。有毒的可能性 环境化学对这种向上趋势的贡献相对尚未探索。有 但是，人类和机械实验室数据表明有机氯农药， 其中的DDT与糖尿病和代谢综合征的风险增加有关。 直到1972年，美国广泛使用了DDT 控制。在培训结束时，候选人将过渡到独立职业 专注于阐明与代谢和代谢相关的围产期暴露机制 内分泌功能障碍。这些研究应该可以更好地理解可能的角色 代谢综合征和糖尿病病因中的环境有毒物质，将建立 候选人未来研究的强烈跨学科基础。