Neonatal exposure to parathion alters lipid metabolism in adulthood: Interactions with dietary fat intake and implications for neurodevelopmental deficits
Neonatal exposure to parathion alters lipid metabolism in adulthood: Interactions with dietary fat intake and implications for neurodevelopmental deficits
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DOI：
10.1016/j.brainresbull.2009.07.002
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发表时间：
2010-01-15
影响因子：
3.8
通讯作者：
Slotkin, Theodore A.
中科院分区：
文献类型：
--
作者：
Lassiter, T. Leon;Ryde, Ian T.;Slotkin, Theodore A.
有机磷酸盐是发育神经毒物，但最近的证据也指出代谢功能障碍。我们确定了新生大鼠暴露于氟磷是否对脂肪因子和脂质过氧化的调节有长期影响。我们还评估了这些影响与脂肪摄入量增加的相互作用。在出生后第1-4天，使用跨越几乎检测不到的胆碱酯酶抑制阈值和全身毒性最初迹象的剂量（0.1或0.2毫克/千克/天），对大鼠给予双硫磷。在成年期，动物要么维持标准食物，要么转为高脂肪饮食7周。我们评估了血清瘦素和脂联素，脂肪组织中的肿瘤坏死因子α（TNF α），外周组织和脑区的硫代巴比妥酸反应物质（TBARS）。新生儿暴露于氟离子使血清瘦素水平与体重无关，抑制脂联素，升高白色脂肪组织中的TNF α。一些影响被高脂肪饮食所抵消。对硫磷降低了脂肪组织、骨骼肌和颞/枕叶皮质中的TBARS，但没有降低心脏、肝脏、肾脏或额叶/顶叶皮质中的TBARS;它升高了小脑中的TBARS;高脂肪饮食再次逆转了许多影响。新生儿暴露于氟离子会破坏脂肪组织和大脑之间传递代谢状态的脂肪因子的调节，同时也会引起炎症性脂肪反应。我们的研究结果与脂肪利用受损和前驱糖尿病一致，并揭示了对脂肪代谢和大脑突触功能影响之间的潜在关系。(C)2009 Elsevier Inc. All rights reserved.
Organophosphates are developmental neurotoxicants but recent evidence also points to metabolic dysfunction. We determined whether neonatal parathion exposure in rats has long-term effects on regulation of adipokines and lipid peroxidation. We also assessed the interaction of these effects with increased fat intake. Rats were given parathion on postnatal days 1-4 using doses (0.1 or 0.2 mg/kg/day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs of systemic toxicity. In adulthood, animals were either maintained on standard chow or switched to a high-fat diet for 7 weeks. We assessed serum leptin and adiponectin, tumor necrosis factor-alpha (TNF alpha) in adipose tissues, and thiobarbituric acid reactive species (TBARS) in peripheral tissues and brain regions. Neonatal parathion exposure uncoupled serum leptin levels from their dependence on body weight, suppressed adiponectin and elevated TNFa in white adipose tissue. Some of the effects were offset by a high-fat diet. Parathion reduced TBARS in the adipose tissues, skeletal muscle and temporal/occipital cortex but not in heart, liver, kidney or frontal/parietal cortex; it elevated TBARS in the cerebellum; the high-fat diet again reversed many of the effects. Neonatal parathion exposure disrupts the regulation of adipokines that communicate metabolic status between adipose tissues and the brain, while also evoking an inflammatory adipose response. Our results are consistent with impaired fat utilization and prediabetes, as well as exposing a potential relationship between effects on fat metabolism and on synaptic function in the brain. (C) 2009 Elsevier Inc. All rights reserved.