Effect of biological sex on human circulating lipidome: An overview of the literature

Cardiovascular diseases (CVD) are the leading cause of death worldwide for both men and women, but their prevalence and burden show marked sex differences. The existing knowledge gaps in research, prevention, and treatment for women emphasize the need for understanding the biological mechanisms contributing to the sex differences in CVD. Sex differences in the plasma lipids that are well-known risk factors and predictors of CVD events have been recognized and are believed to contribute to the known disparities in CVD manifestations in men and women. However, the current understanding of sex differences in lipids has mainly come from the studies on routinely measured standard lipids-low-density lipoprotein cholesterol (LDL-C), high-density lipo-protein cholesterol (HDL-C), total triglycerides, and total cholesterol, which have been the mainstay of the lipid profiling. Sex differences in individual lipid species, collectively called the lipidome, have until recently been less explored due to the technological challenges and analytic costs. With the technological advancements in the last decade and growing interest in understanding mechanisms of sexual dimorphism in metabolic disorders, many investigators utilized metabolomics and lipidomics based platforms to examine the effect of biological sex on detailed lipidomic profiles and individual lipid species. This review presents an overview of the research on sex differences in the concentrations of circulating lipid species, focusing on findings from the metabolome-and lipidome-wide studies. We also discuss the potential contribution of genetic factors including sex chromosomes and sex-specific physiological factors such as menopause and sex hormones to the sex differences in lipidomic profiles.