Association between PFAS exposure and metabolic-related biomarkers in Spanish adolescents

Per- and polyfluoroalkyl substances (PFAS) exert endocrine disruptive effects on the endocrine-metabolic axis. Emerging knowledge suggests that kisspeptin may play a key role in these effects.

To assess the cross-sectional association of blood PFAS concentrations with kisspeptin levels, KISS1 gene DNA methylation, and metabolic-related biomarkers in adolescent males from the Spanish INMA-Granada cohort.

Seven PFAS and twelve biomarkers (glucose-GLU, total cholesterol-TC, triglycerides, LDL, HDL, ALP, AST, ALT, GGT, total bilirubin-BILT, direct bilirubin-BILD, and urea) were measured in plasma and serum, respectively, from 129 adolescent males (15-17 yrs). Systolic and diastolic blood pressure (SBP, DBP), pulse, z-scored body mass index, kisspeptin protein levels (n = 104) and whole blood KISS1 DNA methylation (n = 117) were determined. Linear regression models, weighted quantile sum (WQS), and Bayesian kernel machine (BKMR) were fit.

PFHpA was associated with lower GLU levels [% change per log-unit increase in plasma concentrations (95%CI) = -4.73 (-8.98;-0.28)], and PFUnDA with higher GLU, TC, and HDL levels. In models adjusted by kisspeptin level, PFOS was associated with higher SBP [3.42 (-0.12; 7.09)]. Additionally, PFNA and total PFAS concentrations were associated with higher kisspeptin levels [3.91 (0.55; 7.37) and 6.14 (0.47; 12.13), respectively]. Mixture models showed that combined PFAS exposure was associated with higher HDL, lower hepatic biomarkers (ALT, BILD) and higher kisspeptin levels.

Certain PFAS (e.g. PFUnDA) and their mixture were associated with metabolic-related biomarkers, mainly GLU, HDL, and SBP. These associations may be influenced by kisspeptin levels. More studies are needed to verify these observations.