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: 8610309
• 负责人: Michele A La Merrill
• 金额: $ 24.76万
• 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/8610309
• 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.

项目概要 候选人寻求基于跨学科培训的职业发展支持 在毒理学和环境流行病学领域，使她能够推进她的科学事业 通过调查生命早期接触 DDT 对代谢风险的可能贡献 综合症和糖尿病。科学目标是检验以下假设：围产期暴露于 DDT 以剂量依赖性方式增加老年人患代谢综合征的风险。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 MENTORED PHASE）将纳入动态体内生理学 医学领域开发的代谢示踪剂和正常血糖钳夹等技术 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）将涉及对现在中年妇女的女儿进行跟踪 参加了加州儿童健康与发展研究出生队列研究的人 40 多年前，将涉及代际生命历程分析。独立者 该阶段将以寻求识别 DDT 代谢毒性生物标志物的研究结束 老鼠。代谢综合征通常与肥胖和糖尿病相关，影响着超过 4700 万人 美国居民。过去十年中患病率迅速增加。有毒的可能性 环境化学品对这一上升趋势的贡献相对尚未被探索。有 然而，人体和机械实验室数据表明有机氯农药， 其中滴滴涕与糖尿病和代谢综合征的风险增加有关。 1972 年之前，DDT 在美国被广泛使用，并且在世界范围内仍然大量用于治疗疟疾 控制。培训结束后，候选人将过渡到独立职业 重点是阐明涉及代谢和代谢的围产期暴露机制 内分泌功能失调。这些研究应该有助于更好地理解可能的作用 环境毒物在代谢综合征和糖尿病病因学中的作用，并将建立 为候选人未来的研究奠定强有力的跨学科基础。