Perfluorooctane sulfonatepromotes hepatic lipid accumulation and steatosis in high-fat diet mice through AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) pathway
Perfluorooctane sulfonatepromotes hepatic lipid accumulation and steatosis in high-fat diet mice through AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK/ACC) pathway
复制标题
全氟辛烷磺酸通过AMP激活蛋白激酶/乙酰辅酶A羧化酶(AMPK/ACC)途径促进高脂饮食小鼠肝脏脂质积累和脂肪变性
DOI：
10.1002/jat.4383
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发表时间：
2022-09-14
影响因子：
3.3
通讯作者：
Zhao，Jianya
中科院分区：
文献类型：
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作者：
Ling，Junyi;Hua，Lu;Zhao，Jianya
全氟辛烷磺酸（PFOS）是一种具有肝毒性的环境有机污染物，可引起肝脏异常脂质积累。然而，PFOS诱导肝脂肪变性的分子机制尚不清楚。我们的研究表明，亚慢性全氟辛烷磺酸暴露抑制AMP激活的蛋白激酶（AMPK）磷酸化，导致乙酰辅酶a羧化酶（ACC）活性增加，脂肪酸β氧化减弱，从而导致肝脏脂质积累。我们发现，1 mg/kg/天的全氟辛烷磺酸暴露显著加重了高脂饮食（HFD）喂养小鼠的脂肪变性，同时降低了AMPK活性。油红O结果显示，全氟辛烷磺酸暴露导致HepG2细胞脂肪堆积。正如预测的那样，PFOS处理以浓度依赖的方式降低了磷酸化AMPK的水平，导致随后HepG2细胞中ACC活性和脂滴积累的增加。用200 μM AMPK激动剂AICAR处理可减轻PFOS诱导的ACC活化和脂质积累。总之，我们的数据强调了AMPK/ACC通路在PFOS介导的肝脂质代谢紊乱中的关键作用。
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.