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

项目摘要/摘要 在女性中，当荷尔蒙发生变化时，代谢综合征(METS)的发生率会增加 促进内脏脂肪堆积和更高的循环炎症标志物。生活方式行为是很好的- 已确定的心脏代谢性疾病的危险因素，但对短期内的可能性知之甚少 在围绝经期/更年期期间改变健康行为以减少炎症和代谢综合征，此时女性更多 可能会寻求医疗保健。邻苯二甲酸酯和苯酚，两类内分泌干扰物(EDCs)被发现 在食品、塑料和个人护理产品中，女性的Met较高，主要是在 横断面研究。炎症是将这些EDC暴露于 蛋氨酸在中年的发育和进展但关于毒物的文献很少考虑健康 作为混杂因素或效果修饰者的行为。因此，评估毒物与其他物质之间的相互作用 生活方式因素--包括饮食、睡眠和体力活动--是理解EDC作用的关键差距 暴露于中年女性的炎症和代谢综合征的发展变化。表观遗传 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 影响表观基因组；即基因表达的可遗传改变，不改变DNA序列本身。 孕期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 通过表观遗传机制--包括衰老--可能容易受到毒物影响的研究较少。 墨西哥早期生命暴露于环境毒物(元素)队列具有独特的地位 解决这些研究差距，考虑到随访时间的长短和对毒物和饮食、睡眠和 体力活动。在600名自怀孕以来跟踪调查的妇女中，现在跨越了围绝经期，我们将 利用2008年成年期的存档数据和生物标本，以及新收集的2个中年人的数据 访问次数超过3年(2019-20年、2022-24年)。具体目标是：1)确定接触苯酚和 成年期邻苯二甲酸酯对中年蛋氨酸代谢综合征发育的影响；2)调查 接触苯酚和邻苯二甲酸盐与炎症机制 在两次中年访问中代谢结果的变化；3)发现了其他将苯酚和 使用表观遗传学方法预测邻苯二甲酸盐暴露于甲硫氨酸和中年进展。大都会队 流行率在全球范围内急剧上升--了解女性接触的EDC的影响 对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的 帮助预防和管理妇女随着年龄增长而患上甲型肝炎的知识。

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.