Transcriptome‐wide RNA sequencing analysis of rat skeletal muscle feed arteries (1156.12)

We employed next generation RNA sequencing (RNA‐Seq) technology to determine the influence of obesity on global gene expression in skeletal muscle feed arteries. Transcriptional profiles of the gasctrocnemius and soleus muscle feed arteries (GFA and SFA, respectively) and aortic endothelial cell‐enriched samples from obese Otsuka Long Evans Tokushima Fatty (OLETF) and lean Long Evans Tokushima Otsuka (LETO) rats were examined. Obesity produced 282 upregulated and 133 downregulated genes in SFA and 163 upregulated and 77 downregulated genes in GFA (false discovery rate < 10%) with an overlap of 93 genes between the arteries. Within LETO, there were 89 upregulated and 114 downregulated genes in the GFA compared to the SFA. There were 244 upregulated and 275 downregulated within OLETF (FDR < 10%) in the GFA compared to the SFA, with an overlap of 76 differentially expressed genes common to both LETO and OLETF in both the GFA and SFA. A total of 396 transcripts were found to be differentially expressed between LETO and OLETF in aortic endothelial cell‐enriched samples. Overall, we found (i) the existence of heterogeneity in the transcriptional profile of the SFA and GFA within healthy LETO rats, (ii) that this between‐vessel heterogeneity was markedly exacerbated within the hyperphagic, obese OLETF rat, and (iii) a greater number of genes whose expression was altered by obesity in the SFA compared to the GFA. Also, results indicate that in OLETF rats, the GFA takes on a relatively more pro‐atherogenic phenotype compared to the SFA. Grant Funding Source : Supported by NIH RO1HL036088, T32‐AR048523, VHA‐CDA2 1299‐02