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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

The network of the upstream regulator FOXO1 by IPA®. Genes presented in red are up-regulated in the high oleic acid content (H) group. Genes presented in green are down-regulated in the H group. The intensity of the colors is related to the estimated of the fold change. The interrupted lines in orange represents direct inhibition. The blue represents direct activation. The gray lines represent the no interactions have been reported in the literature
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Fig5: The network of the upstream regulator FOXO1 by IPA®. Genes presented in red are up-regulated in the high oleic acid content (H) group. Genes presented in green are down-regulated in the H group. The intensity of the colors is related to the estimated of the fold change. The interrupted lines in orange represents direct inhibition. The blue represents direct activation. The gray lines represent the no interactions have been reported in the literature

Mentions: The top five upstream regulators identified from the list of DEGs for CLA-c9t11, associated network functions and toxicology list (list of molecules/genes that are relevant to causality of the phenotype of interest, which can help to identify potential therapeutic or toxicity targets) for CLA-c9t11 content are shown in Additional file 18. Among the top upstream regulators were: interferon, lambda 1 (IFLN1), tumor necrosis factor (TNF), retinoic acid, signal transducer and activator of transcription 2 (STAT2), and interferon regulatory factor 7 (IRF7), which were predicted as activated in this study (see Additional file 19). However other important cytokines and transcription regulators were identified as activated/inhibited such as IFNK (interferon kappa), CCL5 (chemokine (C-C motif) ligand 5) and, PRL (prolactin), TRIM24 (tripartite motif containing 24), NFKB1A (Nuclear factor NF-kappa-B 1A), SREBF1, FOXO1, TP53 and MYC, respectively (see complete list in Additional file 19). Figure 5 shows the FOXO1 network, which has been associated with the metabolic disorder dyslipidemia.Fig. 5


Differences in the skeletal muscle transcriptome profile associated with extreme values of fatty acids content
The network of the upstream regulator FOXO1 by IPA®. Genes presented in red are up-regulated in the high oleic acid content (H) group. Genes presented in green are down-regulated in the H group. The intensity of the colors is related to the estimated of the fold change. The interrupted lines in orange represents direct inhibition. The blue represents direct activation. The gray lines represent the no interactions have been reported in the literature
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: The network of the upstream regulator FOXO1 by IPA®. Genes presented in red are up-regulated in the high oleic acid content (H) group. Genes presented in green are down-regulated in the H group. The intensity of the colors is related to the estimated of the fold change. The interrupted lines in orange represents direct inhibition. The blue represents direct activation. The gray lines represent the no interactions have been reported in the literature
Mentions: The top five upstream regulators identified from the list of DEGs for CLA-c9t11, associated network functions and toxicology list (list of molecules/genes that are relevant to causality of the phenotype of interest, which can help to identify potential therapeutic or toxicity targets) for CLA-c9t11 content are shown in Additional file 18. Among the top upstream regulators were: interferon, lambda 1 (IFLN1), tumor necrosis factor (TNF), retinoic acid, signal transducer and activator of transcription 2 (STAT2), and interferon regulatory factor 7 (IRF7), which were predicted as activated in this study (see Additional file 19). However other important cytokines and transcription regulators were identified as activated/inhibited such as IFNK (interferon kappa), CCL5 (chemokine (C-C motif) ligand 5) and, PRL (prolactin), TRIM24 (tripartite motif containing 24), NFKB1A (Nuclear factor NF-kappa-B 1A), SREBF1, FOXO1, TP53 and MYC, respectively (see complete list in Additional file 19). Figure 5 shows the FOXO1 network, which has been associated with the metabolic disorder dyslipidemia.Fig. 5

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