Yang Daqian, Sun Xiaotong, Wei Xiangjuan, Zhang Boya, Fan Xingpei, Du Haining, Zhu Ruijiao, Oh Yuri, Gu Ning
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Faculty of Education, Wakayama University, Wakayama, Japan.
Food Chem Toxicol. 2023 Feb;172:113563. doi: 10.1016/j.fct.2022.113563. Epub 2022 Dec 15.
Lambda-cyhalothrin (LCT) is a critical synthetic Type II pyrethroid insecticide widely applied. Several studies suggest pyrethroids could induce fat accumulation, promote adipogenesis, and impair liver function. Now, the influences of LCT on the hepatic lipid metabolism and the cellular mechanism is still unknown. AMPK has important function in regulating cellular energy balance. To indicate the potential pathogenesis of liver injury caused by LCT exposure, ICR mice were orally administrated with LCT at a dose of 0.4 mg/kg and 2 mg/kg. The results suggest that LCT induced obesity, dyslipidemia and hepatic steatosis. In addition, LCT also induced oxidative stress, liver function injury, and disorganized structure of the liver. Furthermore, upregulation of PPARγ, FASN, and SREBP1c expression, as well as reduction of PPARα and FGF21 expression, bringing with decreases of phosphorylated ratios of AMPK and ACC were found in LCT-L group. These results indicate that LCT at 0.4 mg/kg could result in dyslipidemia and hepatic steatosis in mice. In addition, activation of AMPK in hepatocytes effectively attenuated the effects of LCT. The detailed mechanism of LCT-induced hepatic steatosis is associated with AMPK and its downsteam genes. Activation of AMPK might be a novel protection against the progression of hepatic steatosis induced by LCT.
高效氯氟氰菊酯（LCT）是一种广泛应用的关键合成II型拟除虫菊酯杀虫剂。多项研究表明，拟除虫菊酯可诱导脂肪堆积、促进脂肪生成并损害肝功能。目前，LCT对肝脏脂质代谢的影响及其细胞机制仍不清楚。AMPK在调节细胞能量平衡方面具有重要作用。为了探究LCT暴露所致肝损伤的潜在发病机制，将0.4mg/kg和2mg/kg剂量的LCT经口给予ICR小鼠。结果表明，LCT可导致肥胖、血脂异常和肝脏脂肪变性。此外，LCT还可诱导氧化应激、肝功能损伤以及肝脏结构紊乱。此外，在LCT-L组中发现PPARγ、FASN和SREBP1c表达上调，以及PPARα和FGF21表达降低，同时AMPK和ACC的磷酸化比率下降。这些结果表明，0.4mg/kg的LCT可导致小鼠血脂异常和肝脏脂肪变性。此外，肝细胞中AMPK的激活有效减弱了LCT的作用。LCT诱导肝脏脂肪变性的详细机制与AMPK及其下游基因有关。AMPK的激活可能是预防LCT诱导的肝脏脂肪变性进展的一种新的保护措施。
