Metabolic Health Risk Among Mid-Life Women: The Roles of Toxicants, Inflammation, and Epigenetics

中年女性的代谢健康风险：毒物、炎症和表观遗传学的作用

基本信息

批准号：
10659071
负责人：
Karen Eileen Peterson
金额：
$ 57.82万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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：
2020-09-25 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10659071
关键词：
Address Adult Affect Age Aging Androgens Atherosclerosis Automobile Driving Behavior Biological Biological Markers Cardiometabolic Disease Chemical Exposure Chromatin Classification Cross-Sectional Studies DNA DNA Methylation DNA Sequence Data Development Diet Endocrine Disruptors Environmental Exposure Epigenetic Process Estrogen decline Exposure to Fatty acid glycerol esters Food Gene Expression Genes Genetic Code Glucose Health Health behavior Healthcare Heritability High Prevalence Hormonal Change Hypertension Incidence Inflammation Inflammatory Knowledge Length Leukocytes Life Life Cycle Stages Life Style Link Lipids Literature Longitudinal Studies Measures Menopause Metabolic Metabolic syndrome Mexico Mitotic Modernization Modification Nature Obesity Outcome Pathway interactions Phenols Physical activity Plastics Positioning Attribute Postmenopause Pregnancy Premenopause Prevalence Prevention Puberty Research Risk Risk Factors Role Serum Sleep Toxic Environmental Substances Toxicant exposure United States Visceral fat Visit Woman archived data burden of illness cardiometabolic risk cardiometabolism cohort dietary early life exposure epigenome follow-up indexing inflammatory marker lifestyle factors middle age offspring personal care products phthalates prevent prospective senescence toxicant trend

项目摘要

PROJECT SUMMARY / ABSTRACT Among women, incidence of metabolic syndrome (MetS) increases in midlife, when hormonal changes promote visceral fat accumulation and higher circulating inflammatory markers. Lifestyle behaviors are well- established risk factors for cardiometabolic disease, but less is known about the potential for short-term changes in health behaviors to reduce inflammation and MetS during peri-/menopause, when women are more likely to seek health care. Phthalates and phenols, 2 classes of endocrine disrupting chemicals (EDCs) found in foods, plastics and personal care products, have been linked to higher MetS among women primarily in cross-sectional studies. Inflammation is one plausible pathway connecting these EDC exposures to the development and progression of MetS in midlife but literature on toxicants infrequently accounts for health behaviors as confounders or effect modifiers. Thus, evaluating the interaction between toxicants and other lifestyle factors--including diet, sleep, and physical activity--is a critical gap in understanding the role of EDC exposures on changes in inflammation and MetS development among women in mid-life. Epigenetic alterations may also serve as biomarkers of EDC-metabolic relationships, since these EDCs have the potential to affect the epigenome; i.e. heritable alterations to gene expression that do not alter the DNA sequence itself. The influence of gestational exposures on the offspring epigenome is well-known, but other life course periods potentially vulnerable to effects of toxicants through epigenetic mechanisms—including aging--are less studied. The Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort is uniquely positioned to address these research gaps, given length of follow up and repeated measures of toxicants and diet, sleep and physical activity. Among 600 women followed since pregnancy who now span peri-/menopausal ages, we will leverage archived data and biospecimens from adulthood in 2008, and newly collected data from 2 mid-life visits over 3 years (2019-20, 2022-24). Specific Aims are to: 1) Ascertain the role of exposure to phenols and phthalates in adulthood on the development and progression of MetS in mid-life; 2) Investigate the inflammatory mechanisms that underlie associations between exposure to phenols and phthalates and changes in metabolic outcomes over 2 mid-life visits; 3) Uncover other biological pathways that link phenol and phthalate exposures prospectively to MetS and progression in midlife using an epigenetics approach. MetS prevalence is increasing dramatically worldwide--understanding the impact of EDCs that women are exposed to daily on midlife cardiometabolic risk and the exact nature of these pathways will provide critical new knowledge to aid in prevention and management of MetS in women as they age.

项目概要/摘要在女性中，当荷尔蒙发生变化时，中年时期代谢综合征 (MetS) 的发病率会增加促进内脏脂肪积累和更高的循环炎症标志物。已确定心脏代谢疾病的危险因素，但人们对短期内的潜在风险知之甚少改变健康行为，以减少围绝经期/更年期期间的炎症和代谢综合征，此时女性更年期邻苯二甲酸盐和苯酚是发现的 2 类内分泌干扰化学物质 (EDC)。食品、塑料和个人护理产品中的代谢物与女性较高的代谢综合征有关，主要是在横断面研究是将这些 EDC 暴露与 EDC 联系起来的一种可能途径。中年代谢综合征的发生和进展，但有关毒物的文献很少解释健康问题因此，评估有毒物质和其他物质之间的相互作用。生活方式因素（包括饮食、睡眠和身体活动）是理解 EDC 作用的一个关键差距中年女性炎症和 MetS 发育变化的暴露。这些改变也可以作为 EDC 代谢关系的生物标志物，因为这些 EDC 具有潜在的潜力影响表观基因组；即基因表达的可遗传改变不会改变DNA序列本身。妊娠暴露对后代表观基因组的影响是众所周知的，但其他生命周期时期通过表观遗传机制（包括衰老）可能容易受到有毒物质影响的研究较少。墨西哥生命早期暴露于环境毒物 (ELEMENT) 队列具有独特的优势考虑到对有毒物质以及饮食、睡眠和睡眠的长期跟踪和重复测量，弥补这些研究空白在 600 名自怀孕以来已跨过围绝经期/更年期年龄的女性中，我们将进行身体活动。利用 2008 年成年期的存档数据和生物样本，以及 2 位中年人新收集的数据为期 3 年的访问（2019-20、2022-24）具体目标是： 1) 确定接触酚类和酚类物质的作用。成年期邻苯二甲酸盐对中年 MetS 发生和进展的影响；2) 调查暴露于酚类和邻苯二甲酸盐之间的炎症机制 2 次中年就诊期间代谢结果的变化；3) 发现与苯酚和苯酚相关的其他生物途径；使用表观遗传学方法前瞻性地研究邻苯二甲酸盐暴露于 MetS 和中年进展。全球范围内的患病率急剧上升——了解女性接触 EDC 的影响每天了解中年心脏代谢风险，这些途径的确切性质将提供重要的新信息帮助预防和管理女性随着年龄增长而发生的代谢综合征的知识。