Perfluorooctansulfonate (PFOS) as a persistent organic pollutant has attracted extensive attention for its lipid metabolism disrupting effects. Exposure to PFOS can cause hepatomegaly and lipoatrophy in BALB/c mice, indicating the disturbed triglyceride (TG) homeostasis in liver and white adipose tissue (WAT), albeit with unknown mechanisms. Considering that glyceroneogenesis is the essential pathway for balancing the TG cycle between WAT and liver, we speculate that PFOS act <i>via</i> glyceroneogenesis inhibition to alter TG metabolism in the two tissues. Combining gene expression, enzyme activity assay and molecular docking analysis, we report here that PFOS can interact with cytosolic phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme of glyceroneogenesis. Specifically, by repression on PEPCK, PFOS can inhibit the glyceroneogenesis process and thus decrease the glyceroneogenesis-derived glycerol level, leading to the reduced re-esterified triglyceride level and causing atrophy in WAT. Moreover, in PFOS-exposed liver tissue, despite that free glycerol and fatty acid released from WAT were being used for triglyceride synthesis, the export of triglyceride was slowed down. This eventually resulted in the continuous lipolysis of WAT and lipid accumulation in the liver. PEPCK can be used as a key biomarker to assess the lipid metabolism disorders induced by other conventional and emerging per- and polyfluoroalkyl substances.

Pefluorooctanesulfonate induces hepatomegaly and lipoatrophy in mice through phosphoenolpyruvate carboxykinase-mediated glyceroneogenesis inhibition

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.