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Deregulation of hepatic lipid metabolism associated with insulin resistance in rats subjected to chronic monocrotophos exposure

机译:对慢性偏霉菌暴露的大鼠胰岛素抗性相关的肝脂代谢的放松管制

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In our previous study, we demonstrated the potential of monocrotophos (MCP), an organophosphorus insecticide (OPI), to induce glucose intolerance, insulin resistance (IR), and dyslipidemia with hyperinsulinemia in rats after chronic exposure. As hyperinsulinemia is likely to exert an impact on hepatic lipid metabolism, we carried out this study to establish the effect of chronic MCP exposure (0.9 and 1.8 mg/kg/day for 180 days) on hepatic lipid metabolism in rats. The state of IR induced by MCP in rats was associated with an increase in the liver lipid content (triglyceride and cholesterol) and expression levels of sterol regulatory element-binding proteins, PPARγ, acetyl-CoA carboxylase, and fatty acid synthase in the liver. Similarly, activities of key enzymes (acetyl-COA carboxylase, fatty acid synthase, lipin 1, malic enzyme, glucose-6-phosphate dehydrogenase, and glycerol-3-phosphate dehydrogenase), which regulate lipogenesis, were enhanced in livers of pesticide-treated rats. A strong correlation was observed between insulin levels, hepatic lipid content, and plasma lipid profile in treated rats. Our study suggests that long-term exposure to OPIs not only has a propensity to induce a state of hyper-insulinemic IR, but it is also associated with augmented hepatic lipogenesis, which may explain dyslipidemia induced by chronic exposure to MCP.
机译:在我们之前的研究中,我们证明了久效磷(MCP)是一种有机磷杀虫剂(OPI),在长期接触后,它可能会在大鼠体内诱发葡萄糖不耐受、胰岛素抵抗(IR)和伴有高胰岛素血症的血脂异常。由于高胰岛素血症可能会对肝脏脂质代谢产生影响,我们开展了这项研究,以确定慢性MCP暴露(0.9和1.8 mg/kg/天,持续180天)对大鼠肝脏脂质代谢的影响。MCP诱导的大鼠IR状态与肝脏脂质含量(甘油三酯和胆固醇)的增加以及肝脏中甾醇调节元件结合蛋白、PPARγ、乙酰辅酶A羧化酶和脂肪酸合成酶的表达水平有关。类似地,在杀虫剂处理的大鼠肝脏中,调节脂肪生成的关键酶(乙酰辅酶A羧化酶、脂肪酸合成酶、脂质1、苹果酸酶、葡萄糖-6-磷酸脱氢酶和甘油-3-磷酸脱氢酶)的活性增强。在接受治疗的大鼠中,胰岛素水平、肝脏脂质含量和血脂谱之间存在强烈的相关性。我们的研究表明,长期暴露于OPIs不仅有诱发高胰岛素血症IR的倾向,而且还与肝脏脂肪生成增加有关,这可能解释了长期暴露于MCP引起的血脂异常。

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