IRS1 and Cognitive impairment: Furthermore, EGCG supplemented to mice significantly ameliorated high-fat high-fructose diet (HFFD)-triggered insulin resistance and postprandial oxidative stress, cognitive defects by upregulating the IRS-1 (insulin-receptor substrate 1)/Akt, Keap/Nrf2 and ERK/BDNF/CREB (brain-derived neurotrophic factor/c-AMP-response element binding protein) transcription pathways [104,105].