High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice.
High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice.
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DOI：
10.1016/j.nbd.2014.03.011
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发表时间：
2014-07
影响因子：
6.1
通讯作者：
Kim SF
中科院分区：
文献类型：
--
作者：
Arnold SE;Lucki I;Brookshire BR;Carlson GC;Browne CA;Kazi H;Bang S;Choi BR;Chen Y;McMullen MF;Kim SF
胰岛素抵抗和代谢综合征的其他特征对认知健康的影响越来越受到认可。为了确定发生这种情况的机制，我们给小鼠喂食极高脂肪饮食（60%千卡脂肪）17天或中度高脂肪饮食（HFD，45%千卡脂肪）8周，并检查脑胰岛素信号转导反应，海马突触树突蛋白表达和空间工作记忆的变化。与正常对照饮食小鼠相比，HFD小鼠的大脑皮质组织具有胰岛素抵抗，如通过离体胰岛素刺激的Akt、S6和GSK 3 β的活化失败所证明的。重要的是，我们发现，在HFD小鼠中，在AMPK激活后，脑IPMK的表达（这是mTOR/Akt信号传导所必需的）仍然降低。HFD小鼠海马表现出丝氨酸磷酸化胰岛素受体底物1（IRS 1-pS 616）（胰岛素抵抗的标志物）表达增加，以及PSD-95（一种富含突触后密度的支架蛋白）和突触足蛋白（一种富含脊柱器官的肌动蛋白相关蛋白）表达减少。空间工作记忆受损的评估减少自发交替在T-迷宫。这些发现表明HFD与端脑胰岛素抵抗和对突触完整性和认知行为的有害影响有关。
Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors.
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影响因子：
64.5
作者：
Chakraborty A;Koldobskiy MA;Bello NT;Maxwell M;Potter JJ;Juluri KR;Maag D;Kim S;Huang AS;Dailey MJ;Saleh M;Snowman AM;Moran TH;Mezey E;Snyder SH
通讯作者：
Snyder SH
Dexras1是一种小的GTPase，是谷氨酸-NMDA神经毒性所必需的。
DOI：
10.1523/jneurosci.1497-12.2013
发表时间：
2013-02-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen Y;Khan RS;Cwanger A;Song Y;Steenstra C;Bang S;Cheah JH;Dunaief J;Shindler KS;Snyder SH;Kim SF
通讯作者：
Kim SF
影响因子：
3.8
作者：
de la Monte SM
通讯作者：
de la Monte SM
影响因子：
5.3
作者：
Abbott, MA;Wells, DG;Fallon, JR
通讯作者：
Fallon, JR
影响因子：
16.2
作者：
Hernandez D;Torres CA;Setlik W;Cebrián C;Mosharov EV;Tang G;Cheng HC;Kholodilov N;Yarygina O;Burke RE;Gershon M;Sulzer D
通讯作者：
Sulzer D