Exposure to perfluoroalkylated substances (PFAS) in relation to fitness, physical activity, and adipokine levels in childhood: The european youth heart study.

BACKGROUND: perfluoroalkylated substances (PFAS) are highly persistent chemicals that are able to alter the human metabolism - potentially via disruption of cell signaling pathways mediated by adipokines. Both adiponectin and leptin are influenced by and exert influence on energy storage and energy expenditure, wherefore associations between PFAS and adipokines may be mediated by fitness and fat mass. OBJECTIVES: the aim of this cross-sectional study was to investigate the association between childhood exposure to PFAS and adipokines (adiponectin and leptin), while considering associations between PFAS and children's level of fitness, physical activity and fat mass to elucidate potential mediation by fitness, physical activity and fat mass. METHODS: 9-year old children from Danish public schools were recruited in the European Youth Heart Study in 1997. For this study only children with valid measures on PFAS (PFOS, PFOA, PFNA, PFDA and PFHxS), adipokines (adiponectin and leptin), fitness, fat mass and co-variates (parity and maternal income) were included (N = 242). Multiple linear regression models with and without conditioning and causal mediation analysis were applied. RESULTS: this study found inverse associations between PFOA, PFDA and PFHxS and leptin. PFOA was positively associated with adiponectin, whereas PFHxS was inversely associated with adiponectin in boys. Latter association seemed to be mediated by fat mass. Associations with leptin showed indirect effects of fitness and fat mass but were unable to demonstrate significant mediation. Neither PFOS nor PFNA were associated with the outcome. DISCUSSION: these results may indicate a favorable leptin profile with increasing PFAS, although the results could be driven by residual negative confounding from socio-economic factors and mediation by fitness and fat mass.