The effects of obesity on organophosphate pesticide-mediated toxicities, including both cholinergic and non-cholinergic targets, have not been fully elucidated. Therefore, the present study was designed to determine if high fat diet intake alters the effects of repeated exposure to chlorpyrifos (CPS) on the activities of both cholinergic and noncholinergic serine hydrolase targets. Male C57BL/6J mice were placed on either standard rodent chow or high fat diet for four weeks with CPS exposure (2.0 mg/kg) for the last 10 days of diet intake. Exposure to CPS did not alter acetylcholinesterase in the central nervous system, but it did significantly inhibit circulating cholinesterase activities in both diet groups. CPS significantly inhibited hepatic carboxylesterase and fatty acid amide hydrolase and this inhibition was significantly greater in high fat fed animals. Additionally, CPS exposure and high fat diet intake downregulated genes involved in hepatic de novo lipogenesis as well as cytochrome P450 enzymes involved in hepatic xenobiotic metabolism. In summary, the present study demonstrates that high fat diet intake potentiates CPS mediated inhibition of both carboxylesterase and fatty acid amide hydrolase in the liver of obese animals following subacute exposure and suggests obesity may be a risk factor for increased non-cholinergic hepatic CPS toxicity.

肥胖对有机磷酸酯农药介导的毒性（包括胆碱能靶标和非胆碱能靶标）的影响尚未完全阐明。因此，本研究旨在确定高脂饮食摄入是否改变了反复暴露于毒死rif（CPS）对胆碱能和非胆碱能丝氨酸水解酶靶标活性的影响。将雄性C57BL / 6J小鼠置于标准啮齿动物饲料或高脂饮食中，在饮食的最后10天中暴露CPS（2.0 mg / kg），持续4周。暴露于CPS不会改变中枢神经系统中的乙酰胆碱酯酶，但确实能显着抑制两个饮食组的循环胆碱酯酶活性。CPS显着抑制肝羧酸酯酶和脂肪酸酰胺水解酶，并且在高脂喂养动物中这种抑制作用明显更大。此外，CPS暴露和高脂肪饮食摄入下调了涉及肝脏新生脂肪形成的基因以及涉及肝异源生物代谢的细胞色素P450酶。总之，本研究表明，高脂饮食摄入可增强CPS介导的亚急性暴露后肥胖动物肝脏中羧酸酯酶和脂肪酸酰胺水解酶的抑制作用，并表明肥胖可能是非胆碱能性肝CPS毒性增加的危险因素。CPS暴露和高脂肪饮食摄入下调了涉及肝脏新生脂肪形成的基因以及涉及肝异源生物代谢的细胞色素P450酶。总之，本研究表明，高脂饮食摄入可增强CPS介导的亚急性暴露后肥胖动物肝脏中羧酸酯酶和脂肪酸酰胺水解酶的抑制作用，并表明肥胖可能是非胆碱能性肝CPS毒性增加的危险因素。CPS暴露和高脂肪饮食摄入下调了涉及肝脏新生脂肪形成的基因以及涉及肝异源生物代谢的细胞色素P450酶。总之，本研究表明，高脂饮食摄入可增强CPS介导的亚急性暴露后肥胖动物肝脏中羧酸酯酶和脂肪酸酰胺水解酶的抑制作用，并表明肥胖可能是非胆碱能性肝CPS毒性增加的危险因素。