Abstract
Perfluorooctane sulfonic acid (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 shows that low-dose PFOS exposure can inhibit AMP-activated protein kinase (AMPK) phosphorylation, leading to increased acetyl-CoA carboxylase (ACC) activity and 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 highlights a crucial role of AMPK/ACC pathway in PFOS-mediated liver lipid metabolism disorders.