Perfluorooctane sulfonate promotes hepatic lipid accumulation and steatosis in high‐fat diet mice through AMP‐activated protein kinase/acetyl‐CoA carboxylase (AMPK/ACC) pathway

Abstract

Perfluorooctane sulfonate (PFOS) is a hepatotoxic environmental organic pollutant that can cause aberrant lipid accumulation in the liver. However, the molecular mechanism underlying PFOS‐induced hepatic steatosis remains unclear. Our research showed that subchronic PFOS exposure inhibited AMP‐activated protein kinase (AMPK) phosphorylation, leading to increased acetyl‐CoA carboxylase (ACC) activity, attenuated fatty acid β‐oxidation, and consequent liver lipid accumulation. We found that 1 mg/kg/day PFOS exposure significantly aggravated steatosis in high‐fat diet (HFD)‐fed mice, along with reduced AMPK activity. Oil Red O results showed that PFOS exposure caused fat accumulation in HepG2 cells. As predicted, PFOS treatment reduced the level of phosphorylated AMPK in a concentration‐dependent manner, leading to subsequent increase in ACC activity and lipid droplet accumulation in HepG2 cells. Treatment with 200‐μM AMPK agonist AICAR alleviated PFOS‐induced ACC activation and lipid accumulation. In summary, our data highlight a crucial role of AMPK/ACC pathway in PFOS‐mediated liver lipid metabolic disorders.