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PFOA/PFOS Facilitated Intestinal Fatty Acid Absorption by Activating the PPARα Pathway: Insights from Organoids Model

Environment & Health 2023 15 citations

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Researchers used lab-grown intestinal organoids to study how the forever chemicals PFOA and PFOS affect fatty acid absorption in the gut. They found that PFOS significantly enhanced the intestine's uptake of fatty acids by activating a specific metabolic pathway, while PFOA had weaker effects. The study provides new insight into how these persistent environmental contaminants may disrupt normal digestive function and contribute to metabolic imbalances.

Study Type Environmental

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) continue to be extensively present in the natural environment and seriously threaten human health. The intestinal tract is the primary organ of PFOA/PFOS exposure due to the consumption of contaminated food and drinking water. However, it remains unclear how PFOA/PFOS affects intestinal function and overall health. The aim of this study was to investigate the influence of PFOA/PFOS on the absorption of fatty acids in the intestine and the underlying mechanisms using three-dimensional (3D) intestinal organoids. Our results showed that PFOS, but not PFOA, could significantly enhance the fatty acid uptake capacity without obvious damage to the organoids. Furthermore, PFOS markedly reduced the protein levels of ChgA in enteroendocrine cells, but with no observed impact on aldolase B+ enterocytes. Mechanistically, exposure to PFOS induced the activation of the peroxisome proliferator-activated receptor (PPAR) α pathway in intestinal organoids, with enhanced expression of PPARα target genes associated with fatty acid metabolism, such as Fabp1 and Cd36 (fatty acid transporter genes), Acox1 and Pdk4 (fatty acid oxidation genes), and Plin2 and Plin3 (lipid droplet synthesis genes). These data suggest that PFOS have the potential to affect the absorption function of the intestinal epithelium through the PPARα pathway, and its effect is much stronger than that of PFOA. Our findings also highlight that organoids can be used as a valuable model for conducting toxicological research on environmental chemicals.

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