Untargeted Metabolomics Reveals Sex Differences In Signatures Of A Healthy Lifestyle

Healthy lifestyles are associated with decreased chronic disease risk and increased life expectancy, yet research on sex-specific metabolic differences in response to lifestyle adherence remains limited. This study used fasted plasma from 52 adults adhering to a healthy lifestyle (LIFE) and 52 control (CON) adults. The LIFE group reported high physical activity (>300 min/week), a healthy diet, nonsmoking status, and a BMI <25. The CON group was sedentary, had poor dietary habits, smoked, and had a BMI ≥30. Untargeted metabolomics analysis was conducted using UHPLC-high resolution mass spectrometry followed by data preprocessing, annotations to in-house physical standards library and public databases, statistics, and mummichog pathway analysis using MetaboAnalyst. Distinct metabolic profiles were revealed between LIFE and CON groups for each sex. Seven enriched pathways in males and ten in females were identified, demonstrating sex-specific metabolic responses to healthy lifestyle behaviors and informing future directions in personalized medicine.