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: 8093822
• 负责人: Michele A La Merrill
• 金额: $ 9.24万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 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 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8093822
• 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; public health relevance; research study; response; trend; uptake

DESCRIPTION (provided by applicant) 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. Public Health Relevance: This research training program examines the influence of exposure to the insecticide DDT during early development on the rise of obesity, diabetes, high cholesterol and high blood pressure. High body burdens of DDT are found among adults born before its ban in the US in 1972 and in persons of all ages who have lived in regions where DDT continues to be used extensively for malaria control. The ultimate goal of this work is to understand the possible contribution of DDT to metabolic syndrome and to use this information to design strategies for the prevention of metabolic syndrome.

描述（由申请人提供） 候选人寻求职业发展支持，这将基于她在毒理学和环境流行病学方面的跨学科培训，使她能够通过调查DDT暴露在早期生活中对代谢综合征和糖尿病的风险的可能贡献来提高自己的科学生涯。科学的目标是检验以下假设：围产期暴露于DDT会以剂量依赖性的方式增加衰老成年人代谢综合征的风险。候选人提出了一系列综合的毒理学和流行病学研究。毒理学研究（K99指导阶段）将在医学内分泌学中开发的动态生理技术（例如代谢示踪剂和尤利科血糖夹），以探索小鼠围产期DDT毒性的特定机制。独立（R00阶段）将涉及40年前在加利福尼亚州参加儿童健康和发展研究的妇女的中年女儿的随访，并将涉及世代相传的生活课程分析。独立阶段将在寻求鉴定小鼠中滴滴涕代谢毒性的生物标志物的研究中得出结论。 代谢综合征通常与肥胖和糖尿病有关，影响了超过4700万的美国居民。 在过去的十年中，患病率迅速增加。有毒环境化学对这种向上趋势的可能性相对尚未探索。但是，有人类和机械实验室数据表明，其中有机氯农药（其中包括DDT）与糖尿病风险增加和代谢综合征的增加有关。直到1972年，滴滴涕一直在美国广泛使用，并且在疟疾控制中仍被广泛使用。 在培训结束时，候选人将过渡到独立职业，重点是阐明围产期暴露于代谢和内分泌功能障碍的机制。这些研究应更好地理解环境有毒物质在代谢综合征和糖尿病病因中的可能作用，并将为候选人的未来研究建立强烈的跨学科基础。 公共卫生相关性：该研究培训计划研究了早期发育过程中暴露于杀虫剂DDT对肥胖，糖尿病，高胆固醇和高血压兴起的影响。 DDT的高体负担是在1972年在美国禁令之前出生的成年人，以及居住在DDT继续广泛用于疟疾控制的地区的各个年龄段的人。这项工作的最终目标是了解滴滴涕对代谢综合征的可能贡献，并使用此信息来设计预防代谢综合征的策略。