Abstract
BackgroundThere are differences in the prevalence and severity of diseases between males, females not taking hormonal contraceptives (non-HC females) and females taking hormonal contraceptives (HC females). The aim of this study was to identify sex-specific differences in the metabolome and its relation to components of the metabolic syndrome in a young adult population.MethodsThe subjects analysed are from the 20-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study. Two hundred fifteen plasma metabolites were analysed in 1021 fasted plasma samples by a targeted liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) metabolomics approach. Principal component analysis between males (n = 550), non-HC females (n = 199) and HC females (n = 269) was applied. Regression analysis with a sex × metabolite concentration interaction was performed on components of the MetS, namely waist circumference, systolic blood pressure, and plasma HDL-C, triglycerides and glucose concentration, as outcome to select the significant metabolites of the interaction. Those selected metabolites were used as predictors in a sex group stratified analysis to compare the different β coefficients and therefore the sex group-dependent associations.ResultsPrincipal component analysis between males, non-HC females, and HC females showed a general discriminating trend between males and HC females. One hundred twenty-seven metabolites were significantly different between males and non-HC females, whereas 97 differed between non-HC females and HC females. Males and non-HC females mainly differed in sphingomyelin, lyso-phosphatidylcholine, acyl-carnitine and amino acid species, whilst non-HC females and HC females mainly differed in phosphatidylcholine, lyso-phosphatidylcholine and acyl-carnitine concentrations. Forty-one metabolites (phosphatidylcholines, sphingomyelines, lyso-phosphatidylcholine) were significantly differently associated with the MetS factors in the different groups.ConclusionsWe have shown clear differences between plasma metabolite concentrations in males, and HC or non-HC females, especially in lyso-phosphatidylcholine, sphingomyelin and phosphatidylcholine, which have been shown to associate with obesity in other studies. The association of these metabolites differed between sexes with components of the metabolic syndrome, which means that development of diseases like obesity and diabetes may differ between the sexes. Our findings highlight the importance of considering sex differences when conducting a metabolomics study and the need to account for the effect of HC usage in females in future studies.
Highlights
There are differences in the prevalence and severity of diseases between males, females not taking hormonal contraceptives and females taking hormonal contraceptives (HC females)
Results for all models and metabolites can be found in the Additional file 1: Table S1 which shows that there were significant differences in the concentrations of high density lipoprotein cholesterol (HDL-C), glucose and triglycerides, Systolic blood pressure (sysBP) and waist circumference (WC) between males and non-HC and HC females
Sex differences in the associations with components of the metabolic syndrome (MetS): analysis of variance In the Anova, we found that 46 metabolites showed a sex interaction with at least one component of the MetS
Summary
There are differences in the prevalence and severity of diseases between males, females not taking hormonal contraceptives (non-HC females) and females taking hormonal contraceptives (HC females). The aim of this study was to identify sex-specific differences in the metabolome and its relation to components of the metabolic syndrome in a young adult population. There is increasing evidence from epidemiological studies that sex and oral contraceptive use in females modulate the development and the severity of cardiovascular disease [1,2,3,4]. Since males and females differ in the development and severity of obesity and insulin resistance, it is likely that differences in their metabolism, as a result of genetic effects and environmentally induced changes, may play an important role. Analysis of the metabolome of males and females could provide insights into the sex-related differences of progression and severity of cardiovascular diseases. The characterisation of hormonal contraceptive usage in females with regards to its potential effect on metabolomic changes is highly underrepresented in current research, a large number of women have been using them since their development in the 1960s [3]
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