Serum free fatty acids mediate the association between metal elements and cardiometabolic diseases

Metal-associated free fatty acids (FFAs) on cardiometabolic diseases have rarely been studied.

To investigate metallomics-FFAs relationship, and identify FFAs as potential mediators linking metals to cardiometabolic diseases.

In a nationally representative survey, 18 metals (blood/serum/urine) and 30 serum FFAs were assessed. Weighted linear regression, least absolute shrinkage selection operator, quantile g-computation and receiver operating characteristic were used to analyze associations between metal exposure and FFAs, with mediation and bioinformatics analyses exploring underlying mechanisms.

Blood selenium (Se), mercury (Hg), lead (Pb); serum copper (Cu), zinc (Zn); and urinary arsenic (As) were positively correlated with FFAs [effect range: 5.74% (95% CI: 2.71, 8.85) to 33.08% (95% CI: 28.73, 37.58)], whereas urinary tungsten, molybdenum, and cobalt showed negative associations [-6.17% (95% CI: -9.54, -2.68) to -9.68% (95% CI: -13.75, -5.42)]. Metal mixture was positively associated with most FFAs [15.66% (95% CI: 0.11, 33.62) to 60.35% (95% CI: 40.19, 83.42)]. Key contributors to FFAs disturbance include serum Cu/Zn, blood Hg/Pb, and urinary As. FFAs (primarily nervonic acid and docosapentaenoic acid) mediated the associations of blood metals (Pb, Hg, Se) and serum Zn with cardiometabolic markers (proportions: 6.98%-84.71%). Inflammatory pathways (e.g., IL-17, TNF) may link metal-induced FFA dysregulation to lipotoxicity and cardiometabolic risk.

Our findings provide exploratory evidence connecting metallomics with FFAs and cardiometabolic diseases, suggesting FFAs as potential biomarkers for metal exposure and cardiometabolic diseases prevention.