EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS
EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS
复制标题
EGCG 通过调节 CNS 中的 IRS/AKT 和 ERK/CREB/BDNF 信号通路改善高脂肪和高果糖引起的认知缺陷
DOI：
10.1096/fj.201700400rr
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发表时间：
2017-11-01
期刊：
影响因子：
4.8
通讯作者：
Liu, Xuebo
中科院分区：
文献类型：
--
作者：
Mi, Yashi;Qi, Guoyuan;Liu, Xuebo
肥胖症是由热量摄入和消耗之间的能量不平衡引起的，已成为一个主要的国际健康负担。肥胖会增加胰岛素抵抗和与年龄相关的认知能力下降的风险，并伴有外周炎症。表没食子儿茶素没食子酸酯（EGCG）是绿色茶中的主要多酚，具有抗氧化、抗炎和心脏保护作用，但其对认知功能障碍的潜在作用却鲜有报道。在这项研究中，我们的目标是调查EGCG治疗对高脂高果糖饮食（HFFD）诱导的胰岛素抵抗和记忆障碍的保护作用。将3月龄C57 BL/6 J小鼠随机分为3组：对照组、HFFD组和HFFD + EGCG组。通过使用Morris水迷宫测试评估记忆丧失，在此期间观察到EGCG预防HFFD引起的记忆损害和神经元损失。与这些结果一致，EGCG减弱HFFD诱导的神经元损伤。值得注意的是，EGCG通过上调胰岛素受体底物-1（IRS-1）/AKT和ERK/cAMP反应元件结合蛋白（CREB）/脑源性神经营养因子（BDNF）信号通路，显著改善胰岛素抵抗和认知障碍。长期HFFD引发的神经炎症通过补充EGCG通过抑制MAPK和NF-kB通路以及炎症介质如TNF-α的表达而恢复。EGCG还通过改善细胞氧化状态和线粒体功能来逆转高糖和葡糖胺诱导的SH-SY 5 Y神经元细胞胰岛素抵抗。据我们所知，这项研究是第一个提供令人信服的证据，证明营养化合物EGCG有潜力改善HFFD引发的学习和记忆丧失。米，Y.，Qi，G.，Fan，R.，乔，Q.，Sun，Y.，高，Y.，Liu，X. EGCG通过调节CNS中IRS/AKT和ERK/CREB/BDNF信号通路来改善高脂肪和高果糖诱导的认知缺陷。
Obesity, which is caused by an energy imbalance between calorie intake and consumption, has become a major international health burden. Obesity increases the risk of insulin resistance and age-related cognitive decline, accompanied by peripheral inflammation. (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, possesses antioxidant, anti-inflammatory, and cardioprotective activities; however, few reports have focused on its potential effect on cognitive disorders. In this study, our goal was to investigate the protective effects of EGCG treatment on insulin resistance and memory impairment induced by a high-fat and high-fructose diet (HFFD). We randomly assigned 3-mo-old C57BL/6Jmice to 3 groups with different diets: control group, HFFD group, and HFFD plus EGCG group. Memory loss was assessed by using the Morris water maze test, during which EGCG was observed to prevent HFFD-elicited memory impairment and neuronal loss. Consistent with these results, EGCG attenuated HFFD-induced neuronal damage. Of note, EGCG significantly ameliorated insulin resistance and cognitive disorder by up-regulating the insulin receptor substrate-1 (IRS-1)/AKT and ERK/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathways. Long-term HFFD-triggered neuroinflammation was restored by EGCG supplementation by inhibiting the MAPK and NF-kB pathways, as well as the expression of inflammatory mediators, such as TNF-alpha. EGCG also reversed high glucose and glucosamine-induced insulin resistance in SH-SY5Y neuronal cells by improving the oxidized cellular status and mitochondrial function. To our knowledge, this study is the first to provide compelling evidence that the nutritional compound EGCG has the potential to ameliorate HFFD-triggered learning and memory loss.-Mi, Y., Qi, G., Fan, R., Qiao, Q., Sun, Y., Gao, Y., Liu, X. EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS.