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高美味食物处理的 Wistar 大鼠海马体和下丘脑 PI3K 和 Akt 信号通路的改变。

Alterations of PI3K and Akt signaling pathways in the hippocampus and hypothalamus of Wistar rats treated with highly palatable food.

机构信息

Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

出版信息

Nutr Neurosci. 2012 Jan;15(1):10-7. doi: 10.1179/1476830511Y.0000000030.

Abstract

BACKGROUND/OBJECTIVES: Highly palatable food (HPF), which is enriched in simple sugars and saturated fat, contributes to obesity and insulin resistance in humans. These metabolic changes are associated with serious complications of the central nervous system, including an elevated risk of cognitive dysfunction. We, herein, treated rats with HPF and then examined the insulin-signaling pathway, in particular, the levels of phosphatidylinositol-3 kinase (PI3K), Akt, and insulin receptor substrate-1 (IRS-1) in the hippocampus and hypothalamus.

METHODS

Adult Wistar rats fed with HPF (heated or not during preparation) for 4 months and then measured the levels of PI3K, Akt, and IRS-1 in the hippocampus and hypothalamus, by western blotting and quantitative real-time polymerase chain reaction.

RESULTS

We observed changes in body weight, glucose intolerance, and lipidemia, confirming that peripheral metabolic alterations were induced using this model. Hippocampal PI3K and hypothalamic Akt were affected in rats that are submitted to chronic exposure to an HPF diet. Moreover, heated HPF caused differentiated alterations in the regulatory subunit of PI3K in the hippocampus.

DISCUSSION

Our data suggest that this diet alters insulin signaling differentially in each brain region, and that hippocampal changes induced by this diet could contribute to the understanding of cognitive impairments that are dependent on the hippocampus.

摘要

背景/目的:高可口性食物(HPF)富含简单糖和饱和脂肪,会导致人类肥胖和胰岛素抵抗。这些代谢变化与中枢神经系统的严重并发症有关,包括认知功能障碍的风险增加。我们在此用 HPF 喂养大鼠,然后检查胰岛素信号通路,特别是海马体和下丘脑内的磷酸肌醇-3 激酶(PI3K)、Akt 和胰岛素受体底物-1(IRS-1)的水平。

方法

成年 Wistar 大鼠用 HPF(制备过程中加热或不加热)喂养 4 个月,然后通过 Western blot 和实时定量聚合酶链反应测量海马体和下丘脑内的 PI3K、Akt 和 IRS-1 水平。

结果

我们观察到体重、葡萄糖耐量和血脂异常的变化,证实使用该模型诱导了外周代谢改变。海马体 PI3K 和下丘脑 Akt 在慢性暴露于 HPF 饮食的大鼠中受到影响。此外,加热的 HPF 导致海马体中 PI3K 的调节亚基发生不同的改变。

讨论

我们的数据表明,这种饮食会在每个脑区以不同的方式改变胰岛素信号,并且这种饮食引起的海马体变化可能有助于理解依赖于海马体的认知障碍。

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