Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition

© 2019 Elsevier Inc. Objectives: High-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 stu...

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Main Authors: Napatsorn Saiyasit, Titikorn Chunchai, Dillon Prus, Kanokphong Suparan, Pansa Pittayapong, Nattayaporn Apaijai, Wasana Pratchayasakul, Jirapas Sripetchwandee, Nipon Chattipakorn, M.D., Ph.D., Siriporn C. Chattipakorn
Format: Journal
Published: 2020
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/68521
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-685212020-04-02T15:29:31Z Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition Napatsorn Saiyasit Titikorn Chunchai Dillon Prus Kanokphong Suparan Pansa Pittayapong Nattayaporn Apaijai Wasana Pratchayasakul Jirapas Sripetchwandee Nipon Chattipakorn, M.D., Ph.D. Siriporn C. Chattipakorn Medicine Nursing © 2019 Elsevier Inc. Objectives: High-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. Methods: Male 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. Results: We 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. Conclusions: These 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. 2020-04-02T15:28:43Z 2020-04-02T15:28:43Z 2020-01-01 Journal 18731244 08999007 2-s2.0-85072711166 10.1016/j.nut.2019.110576 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85072711166&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/68521
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Medicine
Nursing
spellingShingle Medicine
Nursing
Napatsorn Saiyasit
Titikorn Chunchai
Dillon Prus
Kanokphong Suparan
Pansa Pittayapong
Nattayaporn Apaijai
Wasana Pratchayasakul
Jirapas Sripetchwandee
Nipon Chattipakorn, M.D., Ph.D.
Siriporn C. Chattipakorn
Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition
description © 2019 Elsevier Inc. Objectives: High-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. Methods: Male 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. Results: We 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. Conclusions: These 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.
format Journal
author Napatsorn Saiyasit
Titikorn Chunchai
Dillon Prus
Kanokphong Suparan
Pansa Pittayapong
Nattayaporn Apaijai
Wasana Pratchayasakul
Jirapas Sripetchwandee
Nipon Chattipakorn, M.D., Ph.D.
Siriporn C. Chattipakorn
author_facet Napatsorn Saiyasit
Titikorn Chunchai
Dillon Prus
Kanokphong Suparan
Pansa Pittayapong
Nattayaporn Apaijai
Wasana Pratchayasakul
Jirapas Sripetchwandee
Nipon Chattipakorn, M.D., Ph.D.
Siriporn C. Chattipakorn
author_sort Napatsorn Saiyasit
title Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition
title_short Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition
title_full Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition
title_fullStr Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition
title_full_unstemmed Gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition
title_sort gut dysbiosis develops before metabolic disturbance and cognitive decline in high-fat diet–induced obese condition
publishDate 2020
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85072711166&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/68521
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