ABSTRACT
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), a kind of emerging environmental endocrine disruptors, may interfere with the secretion of adipokines and affect fetal metabolic function and intrauterine development. However, the epidemiological evidence is limited and inconsistent. We examined the associations of single and multiple PFAS exposures in utero with adipocytokine concentrations in umbilical cord serum. METHODS: This study included 1111 mother-infant pairs from Sheyang Mini Birth Cohort Study (SMBCS), and quantified 12 PFAS and two adipokine in umbilical cord serum. Generalized linear models (GLMs) and Bayesian Kernel Machine Regression (BKMR) models were applied to estimate the associations of single- and mixed- PFAS exposure with adipokines, respectively. Furthermore, sex-stratification was done in each model to assess the sexually dimorphic effects of PFAS. RESULTS: 10 PFAS were detected with median concentrations (µg/L) ranging from 0.04 to 3.97, (except 2.7% for PFOSA and 1.7% for PFDS, which were excluded). In GLMs, for each doubling increase in PFBS, PFHpA, PFHxS, PFHpS, PFUnDA and PFDoDA, leptin decreased between 14.04% for PFBS and 22.69% for PFHpS (P < 0.05). PFAS, except for PFNA, were positively associated with adiponectin, and for each doubling of PFAS, adiponectin increased between 3.27% for PFBS and 12.28% for PFHxS (P < 0.05). In addition, infant gender modified the associations of PFAS with adipokines, especially the associations of PFBS, PFOA and PFHxS with adiponectin. Similarly, significant associations of PFAS mixtures with leptin and adiponectin were observed in the BKMR models. PFDA, PFOS, PFNA and PFHpS were identified as important contributors. In the sex-stratified analysis of BKMR models, the associations between PFAS mixtures and adipokines were more pronounced in males. CONCLUSIONS: PFAS levels were significantly associated with adipokines in cord serum, suggesting that intrauterine mixture of PFAS exposure may be related to decreased fetal leptin level but increased fetal adiponectin level and the associations may be sex-specific.
Subject(s)
Alkanesulfonic Acids , Environmental Pollutants , Fluorocarbons , Male , Female , Humans , Leptin , Adipokines , Cohort Studies , Bayes Theorem , Adiponectin , Umbilical CordABSTRACT
Trimethylamine-N-oxide (TMAO), a diet-derived cometabolite linked to cardiometabolic disease, has been associated with elevated dietary status, particularly in people with kidney failure and adults with dietary modulations. However, the influence of the current diet on TMAO levels in free-living children has not been adequately described. This study was to explore associations of food compositions and dietary diversity with urinary TMAO and its precursor concentrations. Urinary TMAO and its precursor concentrations of 474 healthy children from the Sheyang Mini Birth Cohort were quantified by ultra-performance liquid chromatography−Q Exactive high-resolution mass spectrometer (UPLC-Q Exactive HRMS). Individual food compositions from 24 h dietary recall data were classified into 20 groups and diversity scores were calculated according to the guidelines of the Food and Agriculture Organization of the United Nations (FAO). Associations of urinary TMAO and its precursors with food compositions and dietary diversity scores were assessed by generalized linear regression models. In models adjusted for potential confounders, urinary TMAO was significantly associated with intakes of fish (ß, regression coefficient = 0.155, p < 0.05) and vegetables (ß = 0.120, p < 0.05). Eggs intake showed positive associations with TMAO's precursors (trimethylamine: ß = 0.179, p < 0.05; choline: ß = 0.181, p < 0.05). No association between meat intake and TMAO was observed, whereas meat and poultry intakes were related to the levels of acetyl-L-carnitine and L-carnitine (ß: 0.134 to 0.293, p < 0.05). The indicators of dietary diversity were positively correlated to TMAO concentration (ß: 0.027 to 0.091, p < 0.05). In this free-living children-based study, dietary factors were related to urinary TMAO and its precursors, especially fish, meat, and eggs. As such, dietary diversity was positively related to the level of TMAO.