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Open AccessArticle

Lipotoxic Injury Differentially Regulates Brain Microvascular Gene Expression in Male Mice

Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, One Shields Ave., The Grove, Rm 1159, Davis, CA 95616, USA
INRA, UNH, Université Clermont Auvergne, 63000 Clermont-Ferrand, France
Author to whom correspondence should be addressed.
Authors Contributed Equally.
Nutrients 2020, 12(6), 1771;
Received: 7 May 2020 / Revised: 5 June 2020 / Accepted: 12 June 2020 / Published: 13 June 2020
(This article belongs to the Special Issue High-Fat High-Saturated Diet)
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. View Full-Text
Keywords: genomics; microvascular; brain; dementia; hyperlipidemia; Western diet; males genomics; microvascular; brain; dementia; hyperlipidemia; Western diet; males
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Nuthikattu, S.; Milenkovic, D.; Rutledge, J.C.; Villablanca, A.C. Lipotoxic Injury Differentially Regulates Brain Microvascular Gene Expression in Male Mice. Nutrients 2020, 12, 1771.

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