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Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice

We examined the effect of chronic high fat diet (HFD) on amyloid deposition and cognition of 12-months old APP23 mice, and correlated the phenotype to brain transcriptome and lipidome. HFD significantly increased amyloid plaques and worsened cognitive performance compared to mice on normal diet (ND)...

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Autores principales: Nam, Kyong Nyon, Mounier, Anais, Wolfe, Cody M., Fitz, Nicholas F., Carter, Alexis Y., Castranio, Emilie L., Kamboh, Hafsa I., Reeves, Valerie L., Wang, Jianing, Han, Xianlin, Schug, Jonathan, Lefterov, Iliya, Koldamova, Radosveta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487356/
https://www.ncbi.nlm.nih.gov/pubmed/28655926
http://dx.doi.org/10.1038/s41598-017-04412-2
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author Nam, Kyong Nyon
Mounier, Anais
Wolfe, Cody M.
Fitz, Nicholas F.
Carter, Alexis Y.
Castranio, Emilie L.
Kamboh, Hafsa I.
Reeves, Valerie L.
Wang, Jianing
Han, Xianlin
Schug, Jonathan
Lefterov, Iliya
Koldamova, Radosveta
author_facet Nam, Kyong Nyon
Mounier, Anais
Wolfe, Cody M.
Fitz, Nicholas F.
Carter, Alexis Y.
Castranio, Emilie L.
Kamboh, Hafsa I.
Reeves, Valerie L.
Wang, Jianing
Han, Xianlin
Schug, Jonathan
Lefterov, Iliya
Koldamova, Radosveta
author_sort Nam, Kyong Nyon
collection PubMed
description We examined the effect of chronic high fat diet (HFD) on amyloid deposition and cognition of 12-months old APP23 mice, and correlated the phenotype to brain transcriptome and lipidome. HFD significantly increased amyloid plaques and worsened cognitive performance compared to mice on normal diet (ND). RNA-seq results revealed that in HFD mice there was an increased expression of genes related to immune response, such as Trem2 and Tyrobp. We found a significant increase of TREM2 immunoreactivity in the cortex in response to HFD, most pronounced in female mice that correlated to the amyloid pathology. Down-regulated by HFD were genes related to neuron projections and synaptic transmission in agreement to the significantly deteriorated neurite morphology and cognition in these mice. To examine the effect of the diet on the brain lipidome, we performed Shotgun Lipidomics. While there was no difference in the total amounts of phospholipids of each class, we revealed that the levels of 24 lipid sub-species in the brain were significantly modulated by HFD. Network visualization of correlated lipids demonstrated overall imbalance with most prominent effect on cardiolipin molecular sub-species. This integrative approach demonstrates that HFD elicits a complex response at molecular, cellular and system levels in the CNS.
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spelling pubmed-54873562017-06-30 Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice Nam, Kyong Nyon Mounier, Anais Wolfe, Cody M. Fitz, Nicholas F. Carter, Alexis Y. Castranio, Emilie L. Kamboh, Hafsa I. Reeves, Valerie L. Wang, Jianing Han, Xianlin Schug, Jonathan Lefterov, Iliya Koldamova, Radosveta Sci Rep Article We examined the effect of chronic high fat diet (HFD) on amyloid deposition and cognition of 12-months old APP23 mice, and correlated the phenotype to brain transcriptome and lipidome. HFD significantly increased amyloid plaques and worsened cognitive performance compared to mice on normal diet (ND). RNA-seq results revealed that in HFD mice there was an increased expression of genes related to immune response, such as Trem2 and Tyrobp. We found a significant increase of TREM2 immunoreactivity in the cortex in response to HFD, most pronounced in female mice that correlated to the amyloid pathology. Down-regulated by HFD were genes related to neuron projections and synaptic transmission in agreement to the significantly deteriorated neurite morphology and cognition in these mice. To examine the effect of the diet on the brain lipidome, we performed Shotgun Lipidomics. While there was no difference in the total amounts of phospholipids of each class, we revealed that the levels of 24 lipid sub-species in the brain were significantly modulated by HFD. Network visualization of correlated lipids demonstrated overall imbalance with most prominent effect on cardiolipin molecular sub-species. This integrative approach demonstrates that HFD elicits a complex response at molecular, cellular and system levels in the CNS. Nature Publishing Group UK 2017-06-27 /pmc/articles/PMC5487356/ /pubmed/28655926 http://dx.doi.org/10.1038/s41598-017-04412-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nam, Kyong Nyon
Mounier, Anais
Wolfe, Cody M.
Fitz, Nicholas F.
Carter, Alexis Y.
Castranio, Emilie L.
Kamboh, Hafsa I.
Reeves, Valerie L.
Wang, Jianing
Han, Xianlin
Schug, Jonathan
Lefterov, Iliya
Koldamova, Radosveta
Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice
title Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice
title_full Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice
title_fullStr Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice
title_full_unstemmed Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice
title_short Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice
title_sort effect of high fat diet on phenotype, brain transcriptome and lipidome in alzheimer’s model mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487356/
https://www.ncbi.nlm.nih.gov/pubmed/28655926
http://dx.doi.org/10.1038/s41598-017-04412-2
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