Sex Differences in the Relationships Between Oxidative Stress and Obesity-Related Hormones

Jessica Busler, PhD

Brigham and Women’s Hospital – Fellow
Busler_Jessica poster

Scientific Abstract

Background: Oxidative stress is implicated in obesity and related negative health outcomes such as increased risk for type 2 diabetes mellitus, cardiovascular disease, and psychiatric illnesses. Peripheral studies have shown that a critical factor involved in the mechanistic pathway of oxidative stress is biological sex. Sex differences are also present in concentrations of key obesity-related hormones including leptin and adiponectin. However, sex differences in the relationship between in vivo brain measurements of oxidative stress, such as glutathione (GSH) the primary antioxidant in the brain, and obesity-related hormones has yet to be explored. Thus, we tested the relationship between brain GSH levels with leptin and adiponectin separately in males and females with a range of Body Mass Indexes (BMI).

Methods: 11 women and 13 men, ages 35-61 participated with BMI range 20.4-36.5. MR spectroscopy at 7 Tesla was used to measure markers of GSH in the anterior cingulate (ACC), ventromedial prefrontal (VMPFC), and dorsolateral prefrontal cortices (DLPFC). Peripheral measures of leptin and adiponectin were assayed from a fasted morning blood draw the day of the scan. Relationships between GSH and obesity-related hormones were assessed using Spearman’s rho correlation coefficient.

Results: We observed a significant negative correlation between ACC GSH levels and leptin (rs=-0.58, p=0.048) in men and a significant positive correlation between VMPFC GSH levels and leptin (rs=0.73, p=0.016) in women. DLPFC GSH was also positively related to adiponectin in women (rs=0.83, p=0.003).

Conclusions: This study supports a sex-specific role for oxidative stress in relation to obesity-related hormones involved in energy balance and energy metabolism (i.e. leptin and adiponectin, respectively). Region- and direction-specific findings highlight the importance of considering biological sex in the link between oxidative stress and obesity-related hormones. Taken together, these results have implications for sex differences in brain health with the potential to inform sex-specific antioxidant treatment interventions to improve outcomes in obesity and related conditions.

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research Areas


Jessica N. Busler, PhD, Sarah Rose Slate, BA, Katherine Coleman, MS, Eduardo Coello, PhD, Monica B. Foneska, MS, Vicky Liao, BS, Alexander P. Lin, PhD, Pamela B. Mahon, PhD

Principal Investigator

Pamela B. Mahon, PhD