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

Area of Science:

• Environmental toxicology
• Gastroenterology
• Molecular biology

Background:

• Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) are persistent environmental contaminants posing health risks.
• The intestinal tract is a key site for exposure to PFOA and PFOS through diet.
• The specific effects of PFOA and PFOS on intestinal function remain largely unknown.

Purpose of the Study:

• To investigate the impact of PFOA and PFOS on intestinal fatty acid absorption.
• To elucidate the underlying molecular mechanisms of PFOA/PFOS action in the intestine.
• To evaluate the utility of 3D intestinal organoids as a model for environmental chemical toxicology.

Main Methods:

• Utilized three-dimensional (3D) intestinal organoids derived from human cells.
• Exposed organoids to varying concentrations of PFOA and PFOS.
• Quantified fatty acid uptake, measured protein levels (ChgA, aldolase B), and analyzed gene expression related to fatty acid metabolism (PPARα pathway).

Main Results:

• PFOS significantly increased fatty acid uptake in intestinal organoids without causing apparent damage.
• PFOA did not show a significant effect on fatty acid uptake.
• PFOS reduced ChgA protein levels in enteroendocrine cells but did not affect aldolase B+ enterocytes.
• PFOS exposure activated the PPARα pathway, upregulating target genes involved in fatty acid transport, oxidation, and lipid droplet synthesis (e.g., Fabp1, Cd36, Acox1, Pdk4, Plin2, Plin3).

Conclusions:

• PFOS, but not PFOA, enhances intestinal fatty acid absorption potentially through PPARα pathway activation.
• Organoids serve as a viable model for studying the toxicological effects of environmental chemicals on intestinal function.
• These findings highlight the differential impact of PFOS and PFOA on intestinal physiology and provide mechanistic insights into their effects on fatty acid metabolism.