Short-term high-fat-and-fructose feeding produces insulin signaling alterations accompanied by neurite and synaptic reduction and astroglial activation in the rat hippocampus

Short-term high-fat-and-fructose feeding produces insulin signaling alterations accompanied by neurite and synaptic reduction and astroglial activation in the rat hippocampus
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DOI:
10.1038/jcbfm.2014.48
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发表时间:
2014-06-01
影响因子:
6.3
通讯作者:
Arias, Clorinda
Arias, Clorinda
中科院分区:
医学1区
文献类型:
--
作者:
Calvo-Ochoa, Erika;Hernandez-Ortega, Karina;Arias, Clorinda

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长期食用高脂肪和果糖饮食(HFFD)与胰岛素抵抗(INS)和肥胖的发展有关。长期摄入HFFD引起的全身性胰岛素抵抗会对认知能力、神经发生和长时程增强建立产生不利影响,并伴随着海马神经元的改变。然而,饮食诱导的海马区INS-RES尚未见报道。因此,我们调查了短期高脂饲料喂养是否产生了与海马神经元变化相关的海马胰岛素信号变化。给大鼠喂以对照饲料或在饮用水中添加10%猪油和20%高果糖糖浆的高脂饲料。我们的结果表明,喂养7天的HFFD诱导了肥胖和INS,与海马区的下列变化有关:(1)胰岛素信号减少;(2)海马重量减轻;(3)CA1树突分枝减少和微管相关蛋白2(MAP-2)水平降低;(4)CA1树突棘数量减少,突触素含量减少,tau磷酸化增加;最后,(5)与小胶质细胞变化相关的反应性星形胶质细胞增加。据我们所知,这是第一份关于大鼠海马区胰岛素信号以及短期高脂饲料喂养引起的形态、结构和功能改变的报告。
Chronic consumption of high-fat-and-fructose diets (HFFD) is associated with the development of insulin resistance (Ins Res) and obesity. Systemic insulin resistance resulting from long-term HFFD feeding has detrimental consequences on cognitive performance, neurogenesis, and long-term potentiation establishment, accompanied by neuronal alterations in the hippocampus. However, diet-induced hippocampal Ins Res has not been reported. Therefore, we investigated whether short-term HFFD feeding produced hippocampal insulin signaling alterations associated with neuronal changes in the hippocampus. Rats were fed with a control diet or an HFFD consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water. Our results show that 7 days of HFFD feeding induce obesity and Ins Res, associated with the following alterations in the hippocampus: (1) a decreased insulin signaling; (2) a decreased hippocampal weight; (3) a reduction in dendritic arborization in CA1 and microtubule-associated protein 2 (MAP-2) levels; (4) a decreased dendritic spine number in CA1 and synaptophysin content, along with an increase in tau phosphorylation; and finally, (5) an increase in reactive astrocyte associated with microglial changes. To our knowledge, this is the first report addressing hippocampal insulin signaling, as well as morphologic, structural, and functional modifications due to short-term HFFD feeding in the rat.