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Differential regulation of brain microvessel transcriptome and brain metabolome by Western and heart-healthy dietary patterns in Ossabaw pig

ABSTRACT: Differential regulation of brain microvessel transcriptome and brain metabolome by Western and heart-healthy dietary patterns in Ossabaw pig

PROVIDER: PRJNA1100416 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28681800.fastq.gz	Fastqsanger.gz
	SRR28681801.fastq.gz	Fastqsanger.gz
	SRR28681802.fastq.gz	Fastqsanger.gz
	SRR28681803.fastq.gz	Fastqsanger.gz
	SRR28681804.fastq.gz	Fastqsanger.gz

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Differential regulation of brain microvessel transcriptome and brain metabolome by Western and heart-healthy dietary patterns in Ossabaw pig

Project description:Diet is a potentially modifiable neurodegenerative disease risk factor. We studied the effects of a typical Western diet (WD) relative to a heart-healthy diet (HHD) on microvessel transcriptomics and metabolomics of the brain temporal region in Ossabaw minipigs. Thirty-two pigs (16 male and 16 females) were randomized to the WD or HHD starting at the age of 4 months and were fed the assigned diet for the following 6 months. The WD and HHD were isocaloric and had the same macronutrient content but differed in macronutrient quality. Within each dietary group, half of the pigs also received a statin. Relative to HHD-fed pigs, WD-fed pigs had 2,172 genes differentially expressed (FDR<0.05) by diet, 796 upregulated and 1,376 downregulated. Gene Set Enrichment Analysis identified 22 gene sets enriched in WD, comprising pathways related to inflammation, angiogenesis, and apoptosis, and 53 gene sets enriched in the HHD, including cell energetics, neurotransmission, and inflammation resolution pathways. Enrichment in arginine, tyrosine, and lysine was observed in WD-fed pigs and enrichment in ergothioneine and S-adenosyl methionine in HHD-fed pigs. Statin treatment had very modest effects on brain vessel transcriptome. Our study suggests a likely contribution of diet to brain pathologies characterized by neuroinflammation and neurodegeneration.

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Differential regulation of brain microvessel transcriptome and brain metabolome by western and heart-healthy dietary patterns in Ossabaw pigs.

Project description:Diet is a potentially modifiable neurodegenerative disease risk factor. We studied the effects of a typical Western diet (WD; high in refined carbohydrates, cholesterol and saturated fat), relative to a heart-healthy diet (HHD; high in unrefined carbohydrates, polyunsaturated fat and fiber, and low in cholesterol) on brain microvessel transcriptomics and brain metabolomics of the temporal region in Ossabaw minipigs. Thirty-two pigs (16 male and 16 females) were fed a WD or HHD starting at the age of 4 months for a period of 6 months. The WD and HHD were isocaloric and had a similar macronutrient content but differed in macronutrient quality. Within each dietary group, half of the pigs also received atorvastatin. Relative to HHD-fed pigs, WD-fed pigs had 175 genes differentially expressed (fold change > 1.3, FDR < 0.05) by diet, 46 upregulated and 129 downregulated. Gene Set Enrichment Analysis identified 22 gene sets enriched in WD-fed pigs, comprising pathways related to inflammation, angiogenesis, and apoptosis, and 53 gene sets enriched in the HHD-fed pigs, including cell energetics, neurotransmission, and inflammation resolution pathways. Metabolite analysis showed enrichment in arginine, tyrosine, and lysine in WD-fed pigs, and ergothioneine and S-adenosyl methionine in HHD-fed pigs. Atorvastatin treatment did not affect gene expression. These results suggest a likely contribution of diet to brain pathologies characterized by neuroinflammation and neurodegeneration.

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Project description:SAGE analysis of genes expressed in rat brain microvessels. Keywords: Novel gene identification Microvessels were pooled from 50 rats, a single SAGE library was constructed from the microvessel RNA

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Colon Transcriptome is Modified by a Dietary Pattern/Atorvastatin Interaction in the Ossabaw Pig

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Brain microvessel: Alzheimer disease vs normal

Project description:The enigma that is Alzheimer's disease (AD) continues to present daunting challenges for effective therapeutic intervention. The lack of disease-modifying therapies may, in part, be attributable to the narrow research focus employed to understand this complex disease. Most studies into disease pathogenesis are based on a priori assumptions about the role of AD lesion-associated proteins such as amyloid-? and tau. However, the complex disease processes at work may not be amenable to single-target therapeutic approaches. Genome-wide expression studies provide an unbiased approach for investigating the pathogenesis of complex diseases like AD. A growing literature suggests a role for cerebrovascular contributions to the pathogenesis of AD. The objective of the current study is to examine human brain microvessels isolated from AD patients and controls by microarray analysis. Differentially expressed genes with more than 2-fold change are used for further data analysis. Gene ontology analysis and pathway analysis algorithms within GeneSpringGX are employed to understand the regulatory networks of differentially expressed genes. Twelve matched pairs of AD and control brain microvessel samples are hybridized to Agilent Human 4 × 44 K arrays in replication. We document that more than 2,000 genes are differentially altered in AD microvessels and that a large number of these genes map to pathways associated with immune and inflammatory response, signal transduction, and nervous system development and function categories. These data may help elucidate heretofore unknown molecular alterations in the AD cerebromicrovasculature. Two condition experiment, diseased vs normal, our study included 12 pairs of biological replicates and each pair was repeated with dye swap making total of 24 double channel hybridizations. we excluded 4 samples for not passing QC. So 20 samples were included in the data analysis.

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