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

• 批准号: 10430262
• 负责人: Karen Eileen Peterson
• 金额: $ 57.79万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 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/10430262
• 关键词: Address; Adult; Affect; Age; Aging; Androgens; Atherosclerosis; Automobile Driving; Behavior; Biological; Biological Markers; Cardiometabolic Disease; Chemical Exposure; Chromatin; Cross-Sectional Studies; DNA; DNA Methylation; DNA Sequence; Data; Development; Diet; Endocrine Disruptors; Environmental Exposure; Epigenetic Process; Estrogens; 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; Light; Link; Lipids; Literature; Longitudinal Studies; Measures; Metabolic; Metabolic syndrome; Mexico; Mitotic; Modernization; Modification; Nature; Obesity; Outcome; Pathway interactions; Perimenopause; 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; Women' s Role; archive data; 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

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.

项目摘要 /摘要 在妇女中，荷尔蒙发生变化时，代谢综合征（MetS）的发生率增加 促进内脏脂肪的积累和较高的循环炎症标记。生活方式的行为很好 心脏代谢性疾病的确定危险因素，但对短期的潜力知之甚少 当女性更多时，健康行为的变化减少了感染和大都会大都会 可能寻求医疗保健。发现邻苯二甲酸盐和苯酚，发现两类内分泌破坏化学物质（EDC） 在食品，塑料和个人护理产品方面，与妇女中的较高大都会有关 横断面研究。炎症是连接这些EDC暴露与的合理途径 中年大都会大都会的发展和发展 行为作为混杂因素或效果修饰符。评估有毒物质与其他的相互作用 生活方式因素（包括饮食，睡眠和体育锻炼）是理解EDC作用的关键差距 中年妇女炎症和大都会发育的变化暴露。表观遗传学 改变也可以用作EDC代谢关系的生物标志物，因为这些EDC具有潜力 影响表观基因组；即对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，但是其他生活课程期间 通过表观遗传机制（包括衰老）可能会受到毒物的影响，这很容易受到研究。 墨西哥对环境有毒物质（元素）队列的早期生活暴露是独特的位置 解决这些研究差距，考虑到毒物和饮食，睡眠和重复措施的随访时间和重复措施 体育锻炼。自怀孕以来的600名妇女中，她现在跨越了跨越/绝经年龄的年龄，我们将 从2008年的成年期利用存档的数据和生物测量，并从2个中年开始收集了数据 访问超过3年（2019-20，2022-24）。具体目的是：1）确定暴露于苯酚和 在成年期间，关于中年大都会大都会的发展和发展； 2）调查 暴露于苯酚和邻苯二甲酸盐和邻苯二甲酸盐与 在2次中年访问中，代谢结果的变化； 3）发现其他生物学途径，这些途径将苯酚和 邻苯二甲酸盐使用表观遗传学方法前瞻性地暴露于中年的大都会和进展。大都会 全球范围内的流行率正在急剧增加 - 理解EDC的影响是妇女被暴露 每天都有中年心脏代谢风险和这些途径的确切性质将提供关键的新 知识以帮助预防和管理女性随着年龄的增长。