The Impact of Biological Sex and Circulating Sex Hormones on Oxidative Stress: Implications for Neural Regulation of Obesity
Jessica N. Buslera,b, Sarah Rose Slatea, Eduardo Coelloa, Vicky Liaoa, Alexander P. Lina, Pamela B. Mahona
aReproductive Outcomes of Stress and Aging (ROSA) Center, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA; bHarvard T. H. Chan School of Public Health, Boston, MA, USA
Background: Oxidative stress is implicated in obesity and related negative health outcomes such as increased risk for metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Pre-clinical and peripheral studies suggest that oxidative stress differs by biological sex and covaries with circulating estrogens. However, studies have not yet examined the relationship between biological sex and circulating sex hormones with in vivo measurements of oxidative stress in the brain. Therefore, we tested these relationships with regional concentrations of glutathione (GSH), the primary antioxidant in the brain. Methods: At Brigham & Women’s Hospital (BWH) 10 women and 5 men participated, ages 37-58 (M=46.93, SD=7.19). At Johns Hopkins, 5 women and 7 men participated, ages 35-64 (M=47.83, SD=9.21). MR spectroscopy was used to assess GSH in the anterior cingulate (ACC), ventromedial prefrontal (VMPFC), and dorsolateral prefrontal cortices (DLPFC). Peripheral GSH was assayed at both sites and circulating sex hormones at BWH only. We conducted a z-score meta-analysis to test biological sex differences and regression analyses to test sex hormones in women as predictors of GSH, controlling for age at p<0.05 significance. Results: We observed a significant difference in VMPFC GSH depending on biological sex with males displaying higher levels of GSH in the VMPFC (Figure 1; z=-2.10, p=0.04). We did not observe sex differences in peripheral, ACC, or DLPFC GSH (all p>0.58). Estradiol and estrone were significantly negatively associated (b=-.82, t=-3.45, p=0.01; b=-.74, t=-2.90, p=0.02) with GSH in the ACC, but progesterone was not (p=0.22). No other significant results were observed in for relationships of circulating sex hormones with DLPFC, VMPFC, or peripheral GSH. Conclusions: These results suggest that biological sex and circulating sex hormones in women are key factors to consider in relation to brain oxidative stress in the VMPFC and ACC, regions with altered reactivity in individuals with obesity. Thus, these results advocate for the need to account for the relationship of circulating sex hormones and biological sex with oxidative stress and have the potential to inform clinical care regarding the use of antioxidant or estrogenic medications to improve outcomes in obesity and related conditions.
Breakout Room: Busler, Jessica
View Poster: https://uclacns.org/symposium2021/9-Busler-Jessica.pdf