The effect of PFAS exposure on glucolipid metabolism in children and adolescents: a meta-analysis.

Background: Previous studies showed that per- and polyfluoroalkyl substances (PFAS), which are widely found in the environment, can disrupt endocrine homeostasis when they enter the human body. This meta-analysis aimed to evaluate current human epidemiological evidence on the relationship between PFAS exposure and glucolipid metabolism in childhood and adolescence. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library databases, and identified population-based epidemiological studies related to PFAS and glucolipid metabolism indexes that were published before 30 December 2022. The heterogeneity of the included literature was assessed using the I-square (I2) test and statistics Q. Random-effects and fixed-effects models were used to combine the effect size. Subgroup analysis based on age and sex of the study participants was performed. A sensitivity analysis was used to evaluate the robustness and reliability of the combined results. Egger's and Begg's tests were used to analyze publication bias. Results: A total of 12 studies were included in this analysis. There was a positive association between PFAS and TC (ß = 1.110, 95% CI: 0.601, 1.610) and LDL (ß = 1.900, 95% CI: 1.030, 2.770), and a negative association between PFAS and HOMA-IR in children and adolescents (ß = -0.130, 95% CI: -0. 200, -0.059). PFOS was significant positive associated with TC (ß = 8.22, 95% CI: 3.93, 12.51), LDL (ß = (12.04, 95% CI: 5.08, 18.99), and HOMA-IR (ß = -0.165, 95% CI: -0.292, -0.038). Subgroup analysis showed that exposure to PFAS in the adolescent group was positively associated with TC and LDL levels, and the relationship was stronger in females. Conclusion: PFAS exposure is associated with glucolipid metabolism in children and adolescents. Among them, PFOS may play an important role. Recognition of environmental PFAS exposure is critical for stabilizing the glycolipid metabolism relationship during the growth and development of children and adolescents.

HIF1α elevations at tissue and serum levels and their association with metabolic disorders in obese children.

OBJECTIVE: We aimed to examine the expression profile and circulating level of hypoxia-inducible factor 1 alpha (HIF1α) in children and their relationships with metabolic disorders. METHODS: A total of 519 children were recruited, with paired subcutaneous and omental adipose tissues collected from 17 children and serum samples from the remaining children. All children underwent anthropometric and biochemical analyses. The mRNA, protein, and serum levels of HIF1α were determined by real-time PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. RESULTS: Both HIF1α mRNA and protein levels, especially in omental adipose tissue, increased in overweight or obese (OV/OB) children (p < 0.05). Likewise, serum HIF1α level was remarkably higher in OV/OB children than in normal-weight children (p < 0.05). Serum HIF1α level was positively correlated with BMI z-score, fat mass percentage, waist to height ratio, systolic blood pressure, alanine aminotransferase, total triglycerides, uric acid, and homeostasis model assessment of insulin resistance (IR). Furthermore, a binary logistic regression analysis of serum HIF1α level indicated that the risks for insulin resistance, non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome remained significant in the presence of all potential confounding variables. Finally, the area under the receiver operating characteristic curves for serum HIF1α level in children who were diagnosed with IR, NAFLD, and metabolic syndrome were 0.698 (95% CI, 0.646-0.750; p < 0.001), 0.679 (95% CI, 0.628-0.731; p < 0.001), and 0.900 (95% CI, 0.856-0.945; p < 0.001). CONCLUSION: HIF1α expression is higher in the adipose tissue, especially omental, of obese children than of normal-weight children. Elevated serum HIF1α level is associated with adiposity and metabolic disorder, which may predict a higher risk of obesity complications.