Blood Transcriptome Profiling Reveals Diet-Induced Changes in Metabolic Pathway Gene Expression

Abstract

ObjectivesThis study explored the effects of diet-induced (almonds vs. crackers) changes on blood transcriptome profiles of young adults. MethodsYoung adults (age: 18–22 years) were randomly assigned to consume either almonds (2 oz./d, n = 13) or an isocaloric control snack of graham crackers (325 kcal/d, n = 10) daily for 4 weeks. Blood samples were collected at baseline and 4 weeks after intervention. Total leukocyte RNA was extracted and sequenced. Gene expression profiling was carried out using a 3′ Tag-RNA-Seq protocol. Barcoded sequencing libraries were prepared using the QuantSeq FWD kit for multiplexed sequencing. Data were preprocessed, STAR aligned, and count tables generated using the QuantSeq FWD-UMI pipeline. Differential expression (DE) analysis was conducted on the time x diet model using the limma-voom packages in R. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the DE p-values was conducted using the Wilcoxon rank-sum test in R. P-values were adjusted for false discovery rate correction (FDR). ResultsOut of 13,018 filtered genes, 69 were differentially expressed (FDR < 0.1). Glutamic-oxaloacetic transaminase 2 (GOT2), diacylglycerol kinase alpha (DGKA), and glutaryl-CoA dehydrogenase (GCDH) genes were upregulated with almond consumption. GOT2 plays a role in amino acid metabolism and the urea and tricarboxylic acid cycles, DGKA is involved in lipid metabolism, and GCDH is involved in lysine degradation and tryptophan metabolism. Cracker consumption resulted in greater upregulation of TGF-beta activated kinase 1 gene (MAP3K7) binding protein 3 (TAB3) gene which is involved in the NF-kappaB signal transduction pathway and a greater downregulation in the immunoglobulin superfamily member 8 (IGSF8) gene. Enrichment analyses indicate gene annotations to 341 KEGG pathways. Thermogeneic and ribosomal pathways were significantly enriched (FDR < 0.1). Pathways related to oxidative phosphorylation, sphingolipid signaling, and tryptophan, propanoate, and starch and sucrose metabolism were also differentially enriched (P < 0.05, FDR < 0.3). ConclusionsThese findings indicate that diet (almond vs cracker) potentially alters metabolism through changes in gene transcription. The implications of these findings and associations with health and disease outcomes need to be investigated further. Funding SourcesNIH