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

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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.