Abstract 16786: Sex-Related Differences in Plasma Metabolomic Profiles in Humans
Background: Metabolite profiling has been used to identify biomarkers that may predict common diseases. There are well-documented differences in CVD risk between men and women, though the underlying reasons are not fully understood. Metabolomic profiling may elucidate pathways that are differentially regulated in men vs. women.
Methods: Using LC-MS, we profiled 217 plasma metabolites in Framingham Study participants. We examined the association of log-transformed metabolite levels and sex, in age-adjusted and multivariable-adjusted regression models. To investigate potential mediation by sex hormones, we compared differences in metabolite levels among men, pre-menopausal women, and post-menopausal women receiving or not receiving hormone replacement therapy (HRT). A Bonferroni-adjusted p-value < 0.0002 (0.05/217) was deemed significant.
Results: A total of 1856 individuals free of DM and CVD (mean age, 55; 52% female, 66% post-menopausal) were included. Of 217 metabolites, 101 differed significantly between men and women (60 higher in men, 41 higher in women; each p<0.0002). Glycerol and creatine showed the largest relative differences (>60% higher in women) (Figure, selected metabolites shown). Most amino acids (except glycine and serine) had higher concentrations in men. Hexose sugars and glycerol had higher levels in women. Numerous lipid species differed between men and women. Over one third of metabolites (39%) differed between pre-menopausal and post-menopausal women, and between women taking or not taking HRT, suggesting mediation by estrogen (p<0.0002).
Conclusion: There are widespread sex differences in the human metabolome. These findings underscore differential regulation of multiple metabolic pathways in men and women, and raise the possibility that these metabolic differences may contribute to differences in cardiometabolic disease risk. Our data also highlight the importance of sex when interpreting metabolomic data.
- © 2013 by American Heart Association, Inc.