Mi Yashi, Qi Guoyuan, Fan Rong, Qiao Qinglian, Sun Yali, Gao Yuqi, Liu Xuebo
Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China.
Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China
FASEB J. 2017 Nov;31(11):4998-5011. doi: 10.1096/fj.201700400RR. Epub 2017 Jul 24.
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/6J mice 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-κB pathways, as well as the expression of inflammatory mediators, such as TNF-α. 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.
肥胖是由卡路里摄入与消耗之间的能量失衡引起的，已成为一项重大的国际健康负担。肥胖会增加胰岛素抵抗和与年龄相关的认知衰退风险，并伴有外周炎症。（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶中的主要多酚，具有抗氧化、抗炎和心脏保护活性；然而，很少有报告关注其对认知障碍的潜在影响。在本研究中，我们的目标是研究EGCG治疗对高脂高糖饮食（HFFD）诱导的胰岛素抵抗和记忆障碍的保护作用。我们将3月龄的C57BL/6J小鼠随机分为3组，给予不同饮食：对照组、HFFD组和HFFD加EGCG组。通过莫里斯水迷宫试验评估记忆丧失，在此期间观察到EGCG可预防HFFD引起的记忆障碍和神经元损失。与这些结果一致，EGCG减轻了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/环磷酸腺苷反应元件结合蛋白（CREB）/脑源性神经营养因子（BDNF）信号通路，显著改善了胰岛素抵抗和认知障碍。通过抑制MAPK和NF-κB通路以及炎性介质如TNF-α的表达，补充EGCG可恢复长期HFFD引发的神经炎症。EGCG还通过改善氧化细胞状态和线粒体功能，逆转了SH-SY5Y神经元细胞中高葡萄糖和氨基葡萄糖诱导的胰岛素抵抗。据我们所知，本研究首次提供了令人信服的证据，表明营养化合物EGCG有可能改善HFFD引发的学习和记忆丧失。-米，Y.，齐，G.，范，R.，乔，Q.，孙，Y.，高，Y.，刘，X. EGCG通过调节中枢神经系统中的IRS/AKT和ERK/CREB/BDNF信号通路改善高脂高糖诱导的认知缺陷。
