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

基本信息

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
项目类别：
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

项目摘要

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）该候选人寻求职业发展支持，该支持将建立在她在毒理学和环境流行病学方面的跨学科培训的基础上，使她能够通过调查生命早期接触滴滴涕对代谢综合征和糖尿病风险的可能影响来推进她的科学事业。科学目标是检验以下假设：围产期接触滴滴涕会以剂量依赖性方式增加老年人患代谢综合征的风险。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 MENTORED 阶段）将结合医学内分泌学中开发的代谢示踪剂和正常血糖钳制等动态体内生理技术，以探索小鼠围产期 DDT 毒性的组织特异性机制。独立项目（R00 阶段）将涉及对 40 多年前参加加州儿童健康与发展研究出生队列研究的妇女的中年女儿进行随访，并将涉及代际生命历程分析。独立阶段将以寻求识别小鼠 DDT 代谢毒性生物标志物的研究结束。代谢综合征通常与肥胖和糖尿病相关，影响着超过 4700 万美国居民。过去十年中患病率迅速增加。有毒环境化学物质对这种上升趋势的贡献的可能性相对尚未被探索。然而，人体和机械实验室数据表明，有机氯农药（其中包括滴滴涕）与糖尿病和代谢综合征风险增加有关。 1972 年之前，滴滴涕在美国广泛使用，并且在世界范围内仍然大量用于控制疟疾。培训结束后，候选人将过渡到独立职业，重点是阐明与代谢和内分泌功能障碍有关的围产期暴露机制。这些研究应有助于更好地了解环境毒物在代谢综合征和糖尿病病因学中可能发挥的作用，并将为候选人未来的研究奠定坚实的跨学科基础。公共健康相关性：该研究培训计划探讨了早期发育过程中接触杀虫剂滴滴涕对肥胖、糖尿病、高胆固醇和高血压的影响。在 1972 年美国禁用 DDT 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所有年龄段的人中，DDT 的身体负担较高。这项工作的最终目标是了解滴滴涕对代谢综合征的可能影响，并利用这些信息设计预防代谢综合征的策略。