Serum biomarkers of phthalate exposure, adipose tissue metabolites and 20-years incidence of elevated LDL levels: An exploratory exposome study in the GraMo cohort

Several phthalates are considered metabolic-disrupting chemicals since they may alter adipose tissue and lipid metabolism, although human evidence remains limited. This study explored metabolic signatures in adipose tissue associated with phthalate exposure, and their relationship with the 20-year incidence of elevated low-density lipoprotein (LDL) levels in adults from the GraMo cohort. 72 adipose tissue and serum samples were collected from patients in two public hospitals in Granada, Spain. Adipose tissue was analysed using targeted and non-targeted metabolomic and lipidomic approaches. 32 phthalate biomarkers were measured in serum. LDL levels were obtained from clinical records. A meet-in-the-middle approach identified metabolites associated with both exposure and outcome, with pathway analysis conducted using Mummichog. Phthalates were inversely associated with unsaturated phosphatidylcholines and fatty acids, and positively associated with saturated lipids. These lipid changes were, in turn, linked to elevated LDL incidence. Our findings suggest an impact of lipid metabolism, but warrant further confirmation. • Serum phthalate metabolites and 20-year incidence of high LDL were quantified • Adipose tissue metabolites were analysed using targeted and non-targeted LC-MS/MS • ΣMBPs was linked to higher saturated and lower unsaturated phosphatidylcholines • Saturated phosphatidylcholines were associated with increased risk of high LDL • Unsaturated phosphatidylcholines were associated with decreased risk of high LDL