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Obese mice induced by high-fat diet have differential expression of circular RNAs involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment

Obesity induced by a high-fat diet (HFD) is an important cause of impaired memory and cognitive function, but the underlying mechanisms are not clear. In the present study, we analyzed the levels of circRNAs in the hippocampus of C57BL/6J mice and evaluated the memory and cognition ability of C57BL/...

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Autores principales: Niu, Yan, Chang, Pan, Liu, Tian, Shen, Xi, Zhao, Hui, Zhang, Mingxia, Lei, Shengping, Chen, Baoying, Yu, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574125/
https://www.ncbi.nlm.nih.gov/pubmed/36263377
http://dx.doi.org/10.3389/fnmol.2022.1000482
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author Niu, Yan
Chang, Pan
Liu, Tian
Shen, Xi
Zhao, Hui
Zhang, Mingxia
Lei, Shengping
Chen, Baoying
Yu, Jun
author_facet Niu, Yan
Chang, Pan
Liu, Tian
Shen, Xi
Zhao, Hui
Zhang, Mingxia
Lei, Shengping
Chen, Baoying
Yu, Jun
author_sort Niu, Yan
collection PubMed
description Obesity induced by a high-fat diet (HFD) is an important cause of impaired memory and cognitive function, but the underlying mechanisms are not clear. In the present study, we analyzed the levels of circRNAs in the hippocampus of C57BL/6J mice and evaluated the memory and cognition ability of C57BL/6J mice with HFD using Morris water maze and Y-maze approaches to explore the potential mechanisms linking circRNAs in obesity-associated cognitive impairment. Learning performance showed that HFD-induced obesity mice have impaired memory and cognition. The Arraystar analysis of the hippocampus displayed that HFD-induced obesity leads to the differential expression of circRNAs (DE-circRNAs) in mice. In total, 46 circular RNAs with elevated expression and 10 with decreased expression were identified. Among them, mmu_circRNA_004797 was identified to be significantly downregulated and the expression of mmu_circRNA_21040 was significantly upregulated in the HFD-fed mice, compared with control mice by PCR test. Bioinformatics analysis also showed that the upregulated circRNAs were related to the neuronal function and behavior, and material transport process, while downregulated circRNAs participated in the process of cell response to external stimuli, such as cellular response to nutrient levels. Furthermore, the KEGG pathway analysis showed that the upregulated circRNAs are mainly involved in Axon guidance, calcium signaling pathway, and ErbB signaling pathway. Only a single significant pathway, that is, “protein processing in endoplasmic reticulum”, was observed in the downregulated circRNAs. Finally, we examined the deficits of hippocampal synaptic plasticity and detected the expression of ER stress-related protein. The results showed that ER stress was activated in the hippocampus, and hippocampal synaptic plasticity deficits were displayed. Our results demonstrated that circRNAs were most likely implicated in the predisposition to obesity-associated cognitive impairment.
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spelling pubmed-95741252022-10-18 Obese mice induced by high-fat diet have differential expression of circular RNAs involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment Niu, Yan Chang, Pan Liu, Tian Shen, Xi Zhao, Hui Zhang, Mingxia Lei, Shengping Chen, Baoying Yu, Jun Front Mol Neurosci Molecular Neuroscience Obesity induced by a high-fat diet (HFD) is an important cause of impaired memory and cognitive function, but the underlying mechanisms are not clear. In the present study, we analyzed the levels of circRNAs in the hippocampus of C57BL/6J mice and evaluated the memory and cognition ability of C57BL/6J mice with HFD using Morris water maze and Y-maze approaches to explore the potential mechanisms linking circRNAs in obesity-associated cognitive impairment. Learning performance showed that HFD-induced obesity mice have impaired memory and cognition. The Arraystar analysis of the hippocampus displayed that HFD-induced obesity leads to the differential expression of circRNAs (DE-circRNAs) in mice. In total, 46 circular RNAs with elevated expression and 10 with decreased expression were identified. Among them, mmu_circRNA_004797 was identified to be significantly downregulated and the expression of mmu_circRNA_21040 was significantly upregulated in the HFD-fed mice, compared with control mice by PCR test. Bioinformatics analysis also showed that the upregulated circRNAs were related to the neuronal function and behavior, and material transport process, while downregulated circRNAs participated in the process of cell response to external stimuli, such as cellular response to nutrient levels. Furthermore, the KEGG pathway analysis showed that the upregulated circRNAs are mainly involved in Axon guidance, calcium signaling pathway, and ErbB signaling pathway. Only a single significant pathway, that is, “protein processing in endoplasmic reticulum”, was observed in the downregulated circRNAs. Finally, we examined the deficits of hippocampal synaptic plasticity and detected the expression of ER stress-related protein. The results showed that ER stress was activated in the hippocampus, and hippocampal synaptic plasticity deficits were displayed. Our results demonstrated that circRNAs were most likely implicated in the predisposition to obesity-associated cognitive impairment. Frontiers Media S.A. 2022-10-03 /pmc/articles/PMC9574125/ /pubmed/36263377 http://dx.doi.org/10.3389/fnmol.2022.1000482 Text en Copyright © 2022 Niu, Chang, Liu, Shen, Zhao, Zhang, Lei, Chen and Yu. 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 Molecular Neuroscience
Niu, Yan
Chang, Pan
Liu, Tian
Shen, Xi
Zhao, Hui
Zhang, Mingxia
Lei, Shengping
Chen, Baoying
Yu, Jun
Obese mice induced by high-fat diet have differential expression of circular RNAs involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment
title Obese mice induced by high-fat diet have differential expression of circular RNAs involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment
title_full Obese mice induced by high-fat diet have differential expression of circular RNAs involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment
title_fullStr Obese mice induced by high-fat diet have differential expression of circular RNAs involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment
title_full_unstemmed Obese mice induced by high-fat diet have differential expression of circular RNAs involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment
title_short Obese mice induced by high-fat diet have differential expression of circular RNAs involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment
title_sort obese mice induced by high-fat diet have differential expression of circular rnas involved in endoplasmic reticulum stress and neuronal synaptic plasticity of hippocampus leading to obesity-associated cognitive impairment
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9574125/
https://www.ncbi.nlm.nih.gov/pubmed/36263377
http://dx.doi.org/10.3389/fnmol.2022.1000482
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