Emerging PFAS Exposure Is More Potent in Altering Childhood Lipid Levels Mediated by Mitochondrial DNA Copy Number

Per-
and polyfluoroalkyl substances (PFAS) pose potential
health
risks to lipid metabolism, but the effects of emerging PFAS alternatives,
particularly in children, remain unclear. This cross-sectional study
investigated the association between emerging PFAS exposure and lipid
levels in 294 Chinese children aged 7–10 years, analyzing blood
samples for 14 PFAS and lipid profiles, including triglycerides (TG),
total cholesterol (TC), high-density lipoprotein (HDL), low-density
lipoprotein (LDL), apolipoprotein A1 (ApoA1), and apolipoprotein B
(ApoB). Exposure to 6:2 Cl-PFESA, PFO4DA, and PFO5DoDA was associated
with higher TC, TG, and LDL levels, with PFO4DA increasing the TC
by 1.7% and PFO5DoDA increasing the TG by 10.7%. Weighted quantile
sum (WQS) regression showed mixed PFAS exposure positively associated
with TG (0.08, 95% CI: 0.007, 0.153). PFO4DA had the highest weight
for TC (0.468), TG (0.327), LDL (0.57), ApoA1 (0.243), and ApoB (0.466),
while PFMOAA had the highest weight for HDL (0.332). Bayesian Kernel
Machine Regression (BKMR) analysis confirmed positive associations
between the PFAS mixture and TC, TG, LDL, and ApoA1. Mediation analysis
revealed that mtDNAcn significantly mediated PFAS exposure’s
effect on TG levels, explaining 27.2–74.2% of the total effect.
These findings highlight the need for regulatory action to address
the emerging PFAS risks.