The Western Diet Regulates Hippocampal Microvascular Gene Expression: An Integrated Genomic Analyses in Female Mice

Saivageethi Nuthikattu, Dragan Milenkovic, John Rutledge, Amparo Villablanca

Research output: Contribution to journalArticle

Abstract

Hyperlipidemia is a risk factor for dementia, and chronic consumption of a Western Diet (WD) is associated with cognitive impairment. However, the molecular mechanisms underlying the development of microvascular disease in the memory centers of the brain are poorly understood. This pilot study investigated the nutrigenomic pathways by which the WD regulates gene expression in hippocampal brain microvessels of female mice. Five-week-old female low-density lipoprotein receptor deficient (LDL-R−/−) and C57BL/6J wild type (WT) mice were fed a chow or WD for 8 weeks. Metabolics for lipids, glucose and insulin were determined. Differential gene expression, gene networks and pathways, transcription factors, and non-protein coding RNAs were evaluated by genome-wide microarray and bioinformatics analysis of laser captured hippocampal microvessels. The WD resulted in differential expression of 2,412 genes. The majority of differential gene expression was attributable to differential regulation of cell signaling proteins and their transcription factors, approximately 7% was attributable to differential expression of miRNAs, and a lesser proportion was due to other non-protein coding RNAs, primarily long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs) not previously described to be modified by the WD in females. Our findings revealed that chronic consumption of the WD resulted in integrated multilevel molecular regulation of the hippocampal microvasculature of female mice and may provide one of the mechanisms underlying vascular dementia.

Original languageEnglish (US)
Article number19058
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Gene Expression
Microvessels
Untranslated RNA
T Cell Transcription Factor 1
Small Nucleolar RNA
Long Noncoding RNA
Nutrigenomics
Vascular Dementia
LDL Receptors
Gene Regulatory Networks
Brain
Microarray Analysis
Hyperlipidemias
Computational Biology
MicroRNAs
Dementia
Western Diet
Lasers
Transcription Factors
Genome

ASJC Scopus subject areas

  • General

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The Western Diet Regulates Hippocampal Microvascular Gene Expression : An Integrated Genomic Analyses in Female Mice. / Nuthikattu, Saivageethi; Milenkovic, Dragan; Rutledge, John; Villablanca, Amparo.

In: Scientific reports, Vol. 9, No. 1, 19058, 01.12.2019.

Research output: Contribution to journalArticle

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