• Napatsorn Saiyasit, Titikorn Chunchai, Dillon Prus, Kanokphong Suparan, Pansa Pittayapong, Nattayaporn Apaijai, Wasana Pratchayasakul, Jirapas Sripetchwandee, Nipon Chattipakorn M D Ph D, and Siriporn C Chattipakorn.
• Neurophysiology Unit, Cardiac Electrophysiology Research, and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand.
• Nutrition. 2020 Jan 1; 69: 110576.

ObjectivesHigh-fat diet (HFD) consumption caused metabolic disturbance, gut dysbiosis, brain pathology, microglia hyperactivity, and cognitive decline. However, the exact timeline of these abnormalities following HFD consumption is still elusive. Therefore, the aim of this study was to test the hypothesis that gut dysbiosis, peripheral inflammation, and peripheral insulin resistance occur before the brain inflammatory response, hippocampal synaptic dysplasticity, oxidative stress, apoptosis, and cognitive impairment in HFD-fed rats.MethodsMale Wistar rats received either a normal diet or an HFD for 2, 8, 12, 20, or 40 wk. At the end of each time point, cognitive functions and metabolic parameters were determined. Gut microbiota, brain immune cell activity, amyloid-β level, microglia morphology, hippocampal reactive oxygen species and apoptosis, hippocampal synaptic plasticity, and dendritic spine density were measured.ResultsWe found that HFD-fed rats developed gut dysbiosis at week 2 and peripheral insulin resistance at week 8. Rats fed an HFD for 12 wk displayed hippocampal synaptic dysplasticity, decreased dendritic spine density, an elevation of ionized calcium-binding adapter molecule 1+ cells, increased hippocampal reactive oxygen species levels and hippocampal apoptosis with cognitive decline. The decreased percentage of resident microglia and increased percentage of infiltrated macrophage were observed at weeks 20 and 40. Surprisingly, brain amyloid-β levels were increased after 40 wk of an HFD diet.ConclusionsThese findings demonstrated that gut dysbiosis develops in the earliest phase of consumption of an HFD, followed by brain pathology, which leads to cognitive decline in obese insulin-resistant rats. Therefore, an improvement in gut dysbiosis should provide beneficial effects in the prevention of neuropathology and cognitive decline in the obese.Copyright © 2019 Elsevier Inc. All rights reserved.

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