Lipotoxic Injury Differentially Regulates Brain Microvascular Gene Expression in Male Mice

Hyperlipidemia is a risk factor for vascular disease and dementia, and chronic consumption of a Western Diet (WD) correlates with cognitive impairment. However, the molecular mechanisms are poorly understood. This pilot study used microarrays to investigate the nutrigenomic pathways by which the WD and hyperlipidemia generated in the low-density lipoprotein receptor deficient (LDL-R -/-) male mouse regulate gene expression in the brain hippocampus microvessels. Lipotoxic injury resulted in complex and multilevel molecular regulation of the hippocampal microvasculature involving transcriptional and post transcriptional regulation and may provide a molecular understanding for hyperlipidemia-associated dementia risk. Five-week-old LDL-R-/- (LDLR KO) and C57BL/6J wild type (WT) male mice were fed a chow (control diet, CD) or western diet (WD) for 8 weeks. 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 of pool of n=3 biological replicates per each of the four experimental groups: WT CD, WT WD, LDLR KO CD and LDLR KO WD.