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

Abstract 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...

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Autores principales:	Kyong Nyon Nam, Anais Mounier, Cody M. Wolfe, Nicholas F. Fitz, Alexis Y. Carter, Emilie L. Castranio, Hafsa I. Kamboh, Valerie L. Reeves, Jianing Wang, Xianlin Han, Jonathan Schug, Iliya Lefterov, Radosveta Koldamova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/64ca326a54614325ad15ea64352b2c25
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spelling	oai:doaj.org-article:64ca326a54614325ad15ea64352b2c252021-12-02T15:06:27ZEffect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice10.1038/s41598-017-04412-22045-2322https://doaj.org/article/64ca326a54614325ad15ea64352b2c252017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04412-2https://doaj.org/toc/2045-2322Abstract 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.Kyong Nyon NamAnais MounierCody M. WolfeNicholas F. FitzAlexis Y. CarterEmilie L. CastranioHafsa I. KambohValerie L. ReevesJianing WangXianlin HanJonathan SchugIliya LefterovRadosveta KoldamovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyong Nyon Nam Anais Mounier Cody M. Wolfe Nicholas F. Fitz Alexis Y. Carter Emilie L. Castranio Hafsa I. Kamboh Valerie L. Reeves Jianing Wang Xianlin Han Jonathan Schug Iliya Lefterov Radosveta Koldamova Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice
description	Abstract 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.
format	article
author	Kyong Nyon Nam Anais Mounier Cody M. Wolfe Nicholas F. Fitz Alexis Y. Carter Emilie L. Castranio Hafsa I. Kamboh Valerie L. Reeves Jianing Wang Xianlin Han Jonathan Schug Iliya Lefterov Radosveta Koldamova
author_facet	Kyong Nyon Nam Anais Mounier Cody M. Wolfe Nicholas F. Fitz Alexis Y. Carter Emilie L. Castranio Hafsa I. Kamboh Valerie L. Reeves Jianing Wang Xianlin Han Jonathan Schug Iliya Lefterov Radosveta Koldamova
author_sort	Kyong Nyon Nam
title	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_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_sort	effect of high fat diet on phenotype, brain transcriptome and lipidome in alzheimer’s model mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/64ca326a54614325ad15ea64352b2c25
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Effect of high fat diet on phenotype, brain transcriptome and lipidome in Alzheimer’s model mice

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