Exposure of neonatal rats to parathion elicits sex-selective reprogramming of metabolism and alters the response to a high-fat diet in adulthood.
Exposure of neonatal rats to parathion elicits sex-selective reprogramming of metabolism and alters the response to a high-fat diet in adulthood.
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DOI：
10.1289/ehp.11673
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发表时间：
2008-11
影响因子：
10.4
通讯作者：
Slotkin, Theodore A.
中科院分区：
文献类型：
--
作者：
Lassiter, T. Leon;Ryde, Ian T.;MacKillop, Emiko A.;Brown, Kathleen K.;Levin, Edward D.;Seidler, Frederic J.;Slotkin, Theodore A.
关键词：
有机磷农药的发育暴露几乎无处不在。这些药剂是神经毒物，但最近的证据也指出对新陈代谢的持久影响。我们给新生大鼠注射了双硫磷。在成年期，我们评估了对体重增加、食物消耗、葡萄糖和脂质稳态的影响，以及与高脂饮食影响的相互作用。新生大鼠在出生后第1-4天服用了氯磷定，剂量（0.1或0.2毫克/千克/天）跨越了几乎检测不到的胆碱酯酶抑制和全身毒性最初迹象的阈值。在成年期，动物要么维持标准实验室食物，要么转为高脂肪饮食7周。在正常饮食的雄性大鼠中，低剂量的氯吡格雷暴露导致体重增加，但也诱发了糖尿病前期状态的迹象，空腹血糖升高，脂肪代谢受损。较高剂量的双硫磷逆转了体重增加，并导致进一步的代谢缺陷。女性对代谢紊乱表现出更大的敏感性，在任何一种剂量下体重减轻，葡萄糖和脂质代谢更不平衡。在0.1 mg/kg/天剂量下，雌性动物在高脂饮食中表现出体重增加;在0.2 mg/kg/天剂量下，这种效应被逆转，并伴随着葡萄糖和脂肪代谢的更大缺陷。新生儿低剂量的维生素E暴露以持续和性别选择性的方式破坏葡萄糖和脂肪的体内平衡。生命早期接触有机磷或其他环境化学物质可能在肥胖和糖尿病发病率增加中发挥作用。
Developmental exposures to organophosphate pesticides are virtually ubiquitous. These agents are neurotoxicants, but recent evidence also points to lasting effects on metabolism. We administered parathion to neonatal rats. In adulthood, we assessed the impact on weight gain, food consumption, and glucose and lipid homeostasis, as well as the interaction with the effects of a high-fat diet. Neonatal 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 lab chow or switched to a high-fat diet for 7 weeks. In male rats on a normal diet, the low-dose parathion exposure caused increased weight gain but also evoked signs of a prediabetic state, with elevated fasting serum glucose and impaired fat metabolism. The higher dose of parathion reversed the weight gain and caused further metabolic defects. Females showed greater sensitivity to metabolic disruption, with weight loss at either parathion dose, and greater imbalances in glucose and lipid metabolism. At 0.1 mg/kg/day parathion, females showed enhanced weight gain on the high-fat diet; This effect was reversed in the 0.2-mg/kg/day parathion group, and was accompanied by even greater deficits in glucose and fat metabolism. Neonatal low-dose parathion exposure disrupts glucose and fat homeostasis in a persistent and sex-selective manner. Early-life toxicant exposure to organophosphates or other environmental chemicals may play a role in the increased incidence of obesity and diabetes.
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影响因子：
10.4
作者：
Eskenazi, Brenda;Marks, Amy R.;Bradman, Asa;Harley, Kim;Barr, Dana B.;Johnson, Caroline;Morga, Norma;Jewell, Nicholas A.
通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
Robson, Mark G.
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.
影响因子：
10.4
作者：
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通讯作者：
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影响因子：
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作者：
Chen, AM;Pennell, ML;Longnecker, MP
通讯作者：
Longnecker, MP