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Differences in the skeletal muscle transcriptome profile associated with extreme values of fatty acids content

View Article: PubMed Central - PubMed

ABSTRACT

Background: Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene expression regulation associated with FA content in cattle.

Results: Skeletal muscle transcriptome analysis of 164 Nellore steers revealed no differentially expressed genes (DEGs, FDR 10%) for samples with extreme values for linoleic acid (LA) or stearic acid (SA), and only a few DEGs for eicosapentaenoic acid (EPA, 5 DEGs), docosahexaenoic acid (DHA, 4 DEGs) and palmitic acid (PA, 123 DEGs), while large numbers of DEGs were associated with oleic acid (OA, 1134 DEGs) and conjugated linoleic acid cis9 trans11 (CLA-c9t11, 872 DEGs). Functional annotation and functional enrichment from OA DEGs identified important genes, canonical pathways and upstream regulators such as SCD, PLIN5, UCP3, CPT1, CPT1B, oxidative phosphorylation mitochondrial dysfunction, PPARGC1A, and FOXO1. Two important genes associated with lipid metabolism, gene expression and cancer were identified as DEGs between animals with high and low CLA-c9t11, specifically, epidermal growth factor receptor (EGFR) and RNPS.

Conclusion: Only two out of seven classes of molecules of FA studied were associated with large changes in the expression profile of skeletal muscle. OA and CLA-c9t11 content had significant effects on the expression level of genes related to important biological processes associated with oxidative phosphorylation, and cell growth, survival, and migration. These results contribute to our understanding of how some FAs modulate metabolism and may have protective health function.

Electronic supplementary material: The online version of this article (doi:10.1186/s12864-016-3306-x) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

Network associated with molecular transport, RNA trafficking and RNA post-transcriptional modification impacted by CLA-c9t11 content. Genes presented in red are up-regulated in the high CLA-c9t11 content (H) group. Genes presented in green are down-regulated in the H group. The intensity of the colors is related to estimate of the fold change. Molecules in white are not in the DE list, but were incorporated into the network through relationships with other molecules
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Fig7: Network associated with molecular transport, RNA trafficking and RNA post-transcriptional modification impacted by CLA-c9t11 content. Genes presented in red are up-regulated in the high CLA-c9t11 content (H) group. Genes presented in green are down-regulated in the H group. The intensity of the colors is related to estimate of the fold change. Molecules in white are not in the DE list, but were incorporated into the network through relationships with other molecules

Mentions: The top five associated network functions detected from the list of CLA-c9t11 DEGs between the groups with extreme values of CLA-c9t11 were related to RNA damage, repair and post-transcriptional modification; developmental disorder; metabolic disorder; lipid metabolism, molecular transport, RNA trafficking and; cell death and survival (see Additional file 18). Figure 6 illustrates the network associated with lipid and nucleic acid metabolism and small molecule biochemistry, which presents epidermal growth factor receptor (EGFR) as a central gene and which was down-regulated in animals with high CLA-c9t11 content (colored in green). Figure 7 shows a network associated with molecular transport, RNA trafficking, RNA post-transcriptional modification that contained ribonucleoproteins (RNPS), which were up-regulated in animals with high CLA-c9t11 content. The top five Toxicology terms were associated with cardiac necrosis/cell death (nominal p-value = 1.18e-06), cardiac hypertrophy (nominal p-value = 2.4e-04), hypoxia-inducible factor signaling (nominal p-value = 3.2e-03), increases liver steatosis (nominal p-value = 3.3e-03) and, PPARA/RXRA activation (nominal p-value = 5.3e-03) (see Additional file 18).Fig. 6


Differences in the skeletal muscle transcriptome profile associated with extreme values of fatty acids content
Network associated with molecular transport, RNA trafficking and RNA post-transcriptional modification impacted by CLA-c9t11 content. Genes presented in red are up-regulated in the high CLA-c9t11 content (H) group. Genes presented in green are down-regulated in the H group. The intensity of the colors is related to estimate of the fold change. Molecules in white are not in the DE list, but were incorporated into the network through relationships with other molecules
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC5120530&req=5

Fig7: Network associated with molecular transport, RNA trafficking and RNA post-transcriptional modification impacted by CLA-c9t11 content. Genes presented in red are up-regulated in the high CLA-c9t11 content (H) group. Genes presented in green are down-regulated in the H group. The intensity of the colors is related to estimate of the fold change. Molecules in white are not in the DE list, but were incorporated into the network through relationships with other molecules
Mentions: The top five associated network functions detected from the list of CLA-c9t11 DEGs between the groups with extreme values of CLA-c9t11 were related to RNA damage, repair and post-transcriptional modification; developmental disorder; metabolic disorder; lipid metabolism, molecular transport, RNA trafficking and; cell death and survival (see Additional file 18). Figure 6 illustrates the network associated with lipid and nucleic acid metabolism and small molecule biochemistry, which presents epidermal growth factor receptor (EGFR) as a central gene and which was down-regulated in animals with high CLA-c9t11 content (colored in green). Figure 7 shows a network associated with molecular transport, RNA trafficking, RNA post-transcriptional modification that contained ribonucleoproteins (RNPS), which were up-regulated in animals with high CLA-c9t11 content. The top five Toxicology terms were associated with cardiac necrosis/cell death (nominal p-value = 1.18e-06), cardiac hypertrophy (nominal p-value = 2.4e-04), hypoxia-inducible factor signaling (nominal p-value = 3.2e-03), increases liver steatosis (nominal p-value = 3.3e-03) and, PPARA/RXRA activation (nominal p-value = 5.3e-03) (see Additional file 18).Fig. 6

View Article: PubMed Central - PubMed

ABSTRACT

Background: Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene expression regulation associated with FA content in cattle.

Results: Skeletal muscle transcriptome analysis of 164 Nellore steers revealed no differentially expressed genes (DEGs, FDR 10%) for samples with extreme values for linoleic acid (LA) or stearic acid (SA), and only a few DEGs for eicosapentaenoic acid (EPA, 5 DEGs), docosahexaenoic acid (DHA, 4 DEGs) and palmitic acid (PA, 123 DEGs), while large numbers of DEGs were associated with oleic acid (OA, 1134 DEGs) and conjugated linoleic acid cis9 trans11 (CLA-c9t11, 872 DEGs). Functional annotation and functional enrichment from OA DEGs identified important genes, canonical pathways and upstream regulators such as SCD, PLIN5, UCP3, CPT1, CPT1B, oxidative phosphorylation mitochondrial dysfunction, PPARGC1A, and FOXO1. Two important genes associated with lipid metabolism, gene expression and cancer were identified as DEGs between animals with high and low CLA-c9t11, specifically, epidermal growth factor receptor (EGFR) and RNPS.

Conclusion: Only two out of seven classes of molecules of FA studied were associated with large changes in the expression profile of skeletal muscle. OA and CLA-c9t11 content had significant effects on the expression level of genes related to important biological processes associated with oxidative phosphorylation, and cell growth, survival, and migration. These results contribute to our understanding of how some FAs modulate metabolism and may have protective health function.

Electronic supplementary material: The online version of this article (doi:10.1186/s12864-016-3306-x) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus