PMID- 28739640 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20191210 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 31 IP - 11 DP - 2017 Nov TI - EGCG ameliorates high-fat- and high-fructose-induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS. PG - 4998-5011 LID - 10.1096/fj.201700400RR [doi] AB - 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-kappaB 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. CI - (c) FASEB. FAU - Mi, Yashi AU - Mi Y AD - Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. FAU - Qi, Guoyuan AU - Qi G AD - Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. FAU - Fan, Rong AU - Fan R AD - Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. FAU - Qiao, Qinglian AU - Qiao Q AD - Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. FAU - Sun, Yali AU - Sun Y AD - Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. FAU - Gao, Yuqi AU - Gao Y AD - Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China. FAU - Liu, Xuebo AU - Liu X AD - Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, China xueboliu@aliyun.com. LA - eng PT - Journal Article DEP - 20170724 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, mouse) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Dietary Carbohydrates) RN - 0 (Dietary Fats) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs1 protein, mouse) RN - 30237-26-4 (Fructose) RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Catechin/*analogs & derivatives/pharmacology MH - Cell Line MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - Dietary Carbohydrates/*adverse effects/pharmacology MH - Dietary Fats/*adverse effects/pharmacology MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Fructose/*adverse effects/pharmacology MH - Insulin Receptor Substrate Proteins/*metabolism MH - Learning Disabilities/chemically induced/*metabolism/pathology MH - MAP Kinase Signaling System/*drug effects MH - Memory Disorders/chemically induced/*metabolism/pathology MH - Mice MH - Proto-Oncogene Proteins c-akt/*metabolism OTO - NOTNLM OT - appetite OT - circadian clock OT - cognitive disorder OT - insulin resistance EDAT- 2017/07/26 06:00 MHDA- 2017/11/29 06:00 CRDT- 2017/07/26 06:00 PHST- 2017/05/03 00:00 [received] PHST- 2017/07/10 00:00 [accepted] PHST- 2017/07/26 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/07/26 06:00 [entrez] AID - fj.201700400RR [pii] AID - 10.1096/fj.201700400RR [doi] PST - ppublish SO - FASEB J. 2017 Nov;31(11):4998-5011. doi: 10.1096/fj.201700400RR. Epub 2017 Jul 24.