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A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling

High-fat diets (HFDs) are related to the incidence of obesity and diabetes, but the effect of high-fat diet-induced brain damage remains to be clarified. In our study, we found that 24 weeks of a HFD effectively induced obesity and a change in fur color in mice. In addition, the mice also exhibited...

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Autores principales: Chen, Fei, Yi, Wen-min, Wang, Sheng-yuan, Yuan, Ming-hao, Wen, Jie, Li, Hong-Yan, Zou, Qian, Liu, Shu, Cai, Zhi-you
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524849/
https://www.ncbi.nlm.nih.gov/pubmed/36188454
http://dx.doi.org/10.3389/fnins.2022.978431
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author Chen, Fei
Yi, Wen-min
Wang, Sheng-yuan
Yuan, Ming-hao
Wen, Jie
Li, Hong-Yan
Zou, Qian
Liu, Shu
Cai, Zhi-you
author_facet Chen, Fei
Yi, Wen-min
Wang, Sheng-yuan
Yuan, Ming-hao
Wen, Jie
Li, Hong-Yan
Zou, Qian
Liu, Shu
Cai, Zhi-you
author_sort Chen, Fei
collection PubMed
description High-fat diets (HFDs) are related to the incidence of obesity and diabetes, but the effect of high-fat diet-induced brain damage remains to be clarified. In our study, we found that 24 weeks of a HFD effectively induced obesity and a change in fur color in mice. In addition, the mice also exhibited deficits in learning and memory. We further found that autophagic flux was impaired in mice after HFD feeding. Hypoxia-inducible factor 1α (HIF-1α) expression was significantly increased in HFD-fed mice, and HFD feeding inhibited adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and induced mechanistic target of rapamycin (mTOR) phosphorylation and p70S6K expression. Treatment of HFD-induced BV2 cell model with palmitic acid (PA) was used to further verify a similar result. We concluded that improving tissue hypoxia or enhancing autophagy through the AMPK/mTOR/p70S6K pathway may be a relevant strategy for improving obesity- and ageing-related disorders.
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spelling pubmed-95248492022-10-01 A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling Chen, Fei Yi, Wen-min Wang, Sheng-yuan Yuan, Ming-hao Wen, Jie Li, Hong-Yan Zou, Qian Liu, Shu Cai, Zhi-you Front Neurosci Neuroscience High-fat diets (HFDs) are related to the incidence of obesity and diabetes, but the effect of high-fat diet-induced brain damage remains to be clarified. In our study, we found that 24 weeks of a HFD effectively induced obesity and a change in fur color in mice. In addition, the mice also exhibited deficits in learning and memory. We further found that autophagic flux was impaired in mice after HFD feeding. Hypoxia-inducible factor 1α (HIF-1α) expression was significantly increased in HFD-fed mice, and HFD feeding inhibited adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and induced mechanistic target of rapamycin (mTOR) phosphorylation and p70S6K expression. Treatment of HFD-induced BV2 cell model with palmitic acid (PA) was used to further verify a similar result. We concluded that improving tissue hypoxia or enhancing autophagy through the AMPK/mTOR/p70S6K pathway may be a relevant strategy for improving obesity- and ageing-related disorders. Frontiers Media S.A. 2022-09-16 /pmc/articles/PMC9524849/ /pubmed/36188454 http://dx.doi.org/10.3389/fnins.2022.978431 Text en Copyright © 2022 Chen, Yi, Wang, Yuan, Wen, Li, Zou, Liu and Cai. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Chen, Fei
Yi, Wen-min
Wang, Sheng-yuan
Yuan, Ming-hao
Wen, Jie
Li, Hong-Yan
Zou, Qian
Liu, Shu
Cai, Zhi-you
A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling
title A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling
title_full A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling
title_fullStr A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling
title_full_unstemmed A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling
title_short A long-term high-fat diet influences brain damage and is linked to the activation of HIF-1α/AMPK/mTOR/p70S6K signalling
title_sort long-term high-fat diet influences brain damage and is linked to the activation of hif-1α/ampk/mtor/p70s6k signalling
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9524849/
https://www.ncbi.nlm.nih.gov/pubmed/36188454
http://dx.doi.org/10.3389/fnins.2022.978431
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