Jessica Busler, PhD






Brigham and Women's Hospital




Jessica N. Busler*, Sarah Rose Slate, Katherine Coleman, Eduardo Coello, Monica B. Foneska, Vicky Liao, Alexander P. Lin, Laura M. Holsen,c, Pamela B. Mahon

Principal Investigator:

Pamela Mahon and Laura Holsen

Sex Differences in the Association of Oxidative Stress with Leptin and Adiponectin

Obesity is higher in women than men and has increased at a faster rate in women than men in the past 10 years. Increased prevalence of obesity puts women at greater risk for obesity-related health conditions including high blood pressure, type 2 diabetes, osteoporosis, and psychiatric illnesses.

Increased obesity in women may, in part, be explained by differences in the relationships between adipokines and oxidative stress in the brain as biological sex is implicated as a critical factor in the mechanistic pathway of oxidative stress and impacts concentrations of adipokines. Oxidative stress is induced by proinflammatory adipokines, such as leptin, and increased oxidative stress suppresses production of anti-inflammatory adipokines including adiponectin. Therefore, identifying sex differences in the link between oxidative stress and obesity-related adipokines is critical for our understanding of women’s brain health and may help explain increased obesity, inform treatment strategies, and improve negative health outcomes in this population.


Oxidative stress is implicated in obesity and related negative health outcomes including increased risk for type 2 diabetes mellitus and cardiovascular disease. 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 obesity-related adipokines including leptin and adiponectin. However, sex differences in the relationships between in vivo brain measurements of oxidative stress, such as glutathione (GSH) the primary antioxidant in the brain, and adipokines has yet to be explored. We tested relationships between brain GSH levels and leptin and adiponectin separately in males and females across a wide body mass index (BMI) range.



11 women and 13 men, ages 35-61 participated with BMI range 20.4-36.5 kg/m2. MR spectroscopy was used to measure 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 adipokines were assessed using Spearman’s rho correlation coefficient.



We observed a significant negative correlation between ACC GSH levels and leptin (rs=-0.58, p=0.048; z=-1.80, p=0.072) in men and a significant positive correlation between VMPFC GSH levels and leptin (rs=0.73, p=0.016; z=-2.21, p=0.027) in women. DLPFC GSH was also positively related to adiponectin in women (rs=0.83, p=0.003; z=-2.91, p=0.003).



This study supports a sex-specific role for oxidative stress in relation to adipokines 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 adipokines. 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.