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哺乳期雌性子代大鼠香烟烟雾暴露:对内源性大麻素和多巴胺能系统的迟发效应。

Cigarette smoke during lactation in rat female progeny: Late effects on endocannabinoid and dopaminergic systems.

机构信息

Endocrine Physiology Laboratory, Department of Physiological Sciences, State University of Rio de Janeiro, 20550-030 Rio de Janeiro, RJ, Brazil.

Neurophysiology Laboratory, Department of Physiological Sciences, State University of Rio de Janeiro, 20550-030 Rio de Janeiro, RJ, Brazil.

出版信息

Life Sci. 2019 Sep 1;232:116575. doi: 10.1016/j.lfs.2019.116575. Epub 2019 Jun 15.

Abstract

AIMS

Maternal smoking is considered a risk factor for childhood obesity. In a rat model of tobacco exposure during breastfeeding, we previously reported hyperphagia, overweight, increased visceral fat and hyperleptinemia in adult female offspring. Obesity and eating disorders are associated with impairment in the endocannabinoid (EC) and dopaminergic (DA) systems. Considering that women are prone to eating disorders, we hypothesize that adult female Wistar rats that were exposed to cigarette smoke (CS) during the suckling period would develop EC and DA systems deregulation, possibly explaining the eating disorder in this model.

MATERIAL AND METHODS

To mimic maternal smoking, from postnatal day 3 to 21, dams and offspring were exposed to a smoking machine, 4×/day/1 h (CS group). Control animals were exposed to ambient air. Offspring were evaluated at 26 weeks of age.

KEY FINDINGS

Concerning the EC system, the CS group had increased expression of diacylglycerol lipase (DAGL) in the lateral hypothalamus (LH) and decreased in the liver. In the visceral adipose tissue, the EC receptor (CB1r) was decreased. Regarding the DA system, the CS group showed higher dopamine transporter (DAT) protein expression in the prefrontal cortex (PFC) and lower DA receptor (D2r) in the arcuate nucleus (ARC). We also assessed the hypothalamic leptin signaling, which was shown to be unchanged. CS offspring showed decreased plasma 17β-estradiol.

SIGNIFICANCE

Neonatal CS exposure induces changes in some biomarkers of the EC and DA systems, which can partially explain the hyperphagia observed in female rats.

摘要

目的

母体吸烟被认为是儿童肥胖的一个危险因素。在哺乳期暴露于烟草的大鼠模型中,我们之前报道过成年雌性后代的多食、超重、内脏脂肪增加和瘦素血症。肥胖和饮食失调与内源性大麻素(EC)和多巴胺能(DA)系统的紊乱有关。鉴于女性更容易出现饮食失调,我们假设哺乳期暴露于香烟烟雾(CS)的成年雌性 Wistar 大鼠会出现 EC 和 DA 系统失调,这可能解释了该模型中的饮食失调。

材料和方法

为了模拟母体吸烟,从产后第 3 天到第 21 天,母鼠及其后代每天 4 次暴露于吸烟机中 1 小时(CS 组)。对照动物暴露于环境空气中。后代在 26 周龄时进行评估。

主要发现

关于 EC 系统,CS 组的外侧下丘脑(LH)中二酰基甘油脂肪酶(DAGL)的表达增加,而肝脏中的表达减少。在内脏脂肪组织中,EC 受体(CB1r)减少。关于 DA 系统,CS 组的前额叶皮质(PFC)中多巴胺转运蛋白(DAT)蛋白表达增加,而弓状核(ARC)中的多巴胺受体(D2r)减少。我们还评估了下丘脑瘦素信号,结果显示其未发生变化。CS 组后代的血浆 17β-雌二醇水平降低。

意义

新生儿 CS 暴露会引起 EC 和 DA 系统的一些生物标志物发生变化,这可以部分解释雌性大鼠中观察到的多食。

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