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Lipotoxic Injury Differentially Regulates Brain Microvascular Gene Expression in
Male Mice.
Authors Nuthikattu S, Milenkovic D, Rutledge JC, Villablanca AC
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Nutrients
Year 2020
Date Published 6/1/2020
Volume : Pages 12 : Not Specified
PubMed Reference 32545722
Abstract The Western diet (WD) and hyperlipidemia are risk factors for vascular disease,
dementia, and cognitive impairment. However, the molecular mechanisms are poorly
understood. This pilot study investigated the genomic pathways by which the WD
and hyperlipidemia regulate gene expression in brain microvessels. Five-week-old
C57BL/6J wild type (WT) control and low-density lipoprotein receptor deficient
(LDL-R-/-) male mice were fed the WD for eight weeks. Differential gene
expression, gene networks and pathways, transcription factors, and non-protein
coding RNAs were evaluated by a genome-wide microarray and bioinformatics
analysis of laser-captured hippocampal microvessels. The WD resulted in the
differential expression of 1972 genes. Much of the differentially expressed gene
(DEG) was attributable to the differential regulation of cell signaling proteins
and their transcription factors, approximately 4% was attributable to the
differential expression of miRNAs, and 10% 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. Lipotoxic injury
resulted in complex and multilevel molecular regulation of the hippocampal
microvasculature involving transcriptional and post-transcriptional regulation
and may provide a molecular basis for a better understanding of
hyperlipidemia-associated dementia risk.


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