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Eicosapentaenoic and Docosahexaenoic Acid-Enriched High Fat Diet Delays Skeletal Muscle Degradation in Mice

View Article: PubMed Central - PubMed

ABSTRACT

Low-grade chronic inflammatory conditions such as ageing, obesity and related metabolic disorders are associated with deterioration of skeletal muscle (SkM). Human studies have shown that marine fatty acids influence SkM function, though the underlying mechanisms of action are unknown. As a model of diet-induced obesity, we fed C57BL/6J mice either a high fat diet (HFD) with purified marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (HFD-ED), a HFD with corn oil, or normal mouse chow for 8 weeks; and used transcriptomics to identify the molecular effects of EPA and DHA on SkM. Consumption of ED-enriched HFD modulated SkM metabolism through increased gene expression of mitochondrial β-oxidation and slow-fiber type genes compared with HFD-corn oil fed mice. Furthermore, HFD-ED intake increased nuclear localization of nuclear factor of activated T-cells (Nfatc4) protein, which controls fiber-type composition. This data suggests a role for EPA and DHA in mitigating some of the molecular responses due to a HFD in SkM. Overall, the results suggest that increased consumption of the marine fatty acids EPA and DHA may aid in the prevention of molecular processes that lead to muscle deterioration commonly associated with obesity-induced low-grade inflammation.

No MeSH data available.


Pathway analysis of the gSkM transcriptome for the comparison of HFD-ED and HFD-corn oil fed mice. The illustration is based on the Kegg pathway database (http://www.genome.jp/kegg/pathway.html). (a) Fatty acid β-oxidation: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (b) Electron transport chain: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (c) Krebs Cycle: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (d) Relative Acc protein levels in HFD-ED (white bars) fed mice was lower than HFD-corn oil (black bars) and there was no difference in the phosphorylation of Acc (p-Acc) protein after 8-weeks diet intervention. * Different at p < 0.05.
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nutrients-08-00543-f001: Pathway analysis of the gSkM transcriptome for the comparison of HFD-ED and HFD-corn oil fed mice. The illustration is based on the Kegg pathway database (http://www.genome.jp/kegg/pathway.html). (a) Fatty acid β-oxidation: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (b) Electron transport chain: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (c) Krebs Cycle: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (d) Relative Acc protein levels in HFD-ED (white bars) fed mice was lower than HFD-corn oil (black bars) and there was no difference in the phosphorylation of Acc (p-Acc) protein after 8-weeks diet intervention. * Different at p < 0.05.

Mentions: Eight gene transcripts were upregulated by HFD-ED compared with the HFD-corn oil fed mice (Figure 1a). Functionally, the enzymes in the β-oxidation pathway facilitate the breakdown of fatty acids to form acetyl-CoA, which enters the Krebs cycle. The upregulated gene products, which are responsible for transporting fatty acids into the mitochondria, were two carnitine palmitoyltransferases (Cpt1a and Cpt2). In addition, RNA transcription of genes responsible for the subsequent degradation of fatty acids within the mitochondrial matrix producing acetyl-CoA including short/medium chain acyl-CoA dehydrogenase (Acadm), long chain acyl-CoA dehydrogenase (Acadl), very long chain acyl-CoA dehydrogenase (Acadvl), acetyl-CoA acyl transferase 2 (Acaa2), enoyl-CoA delta isomerase 1 (Eci1) and aldehyde dehydrogenese (Aldh2), were upregulated by the HFD-ED diet.


Eicosapentaenoic and Docosahexaenoic Acid-Enriched High Fat Diet Delays Skeletal Muscle Degradation in Mice
Pathway analysis of the gSkM transcriptome for the comparison of HFD-ED and HFD-corn oil fed mice. The illustration is based on the Kegg pathway database (http://www.genome.jp/kegg/pathway.html). (a) Fatty acid β-oxidation: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (b) Electron transport chain: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (c) Krebs Cycle: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (d) Relative Acc protein levels in HFD-ED (white bars) fed mice was lower than HFD-corn oil (black bars) and there was no difference in the phosphorylation of Acc (p-Acc) protein after 8-weeks diet intervention. * Different at p < 0.05.
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Related In: Results  -  Collection

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nutrients-08-00543-f001: Pathway analysis of the gSkM transcriptome for the comparison of HFD-ED and HFD-corn oil fed mice. The illustration is based on the Kegg pathway database (http://www.genome.jp/kegg/pathway.html). (a) Fatty acid β-oxidation: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (b) Electron transport chain: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (c) Krebs Cycle: Genes highlighted in red are upregulated in gSkM of mice fed HFD-ED compared with HFD-corn oil; (d) Relative Acc protein levels in HFD-ED (white bars) fed mice was lower than HFD-corn oil (black bars) and there was no difference in the phosphorylation of Acc (p-Acc) protein after 8-weeks diet intervention. * Different at p < 0.05.
Mentions: Eight gene transcripts were upregulated by HFD-ED compared with the HFD-corn oil fed mice (Figure 1a). Functionally, the enzymes in the β-oxidation pathway facilitate the breakdown of fatty acids to form acetyl-CoA, which enters the Krebs cycle. The upregulated gene products, which are responsible for transporting fatty acids into the mitochondria, were two carnitine palmitoyltransferases (Cpt1a and Cpt2). In addition, RNA transcription of genes responsible for the subsequent degradation of fatty acids within the mitochondrial matrix producing acetyl-CoA including short/medium chain acyl-CoA dehydrogenase (Acadm), long chain acyl-CoA dehydrogenase (Acadl), very long chain acyl-CoA dehydrogenase (Acadvl), acetyl-CoA acyl transferase 2 (Acaa2), enoyl-CoA delta isomerase 1 (Eci1) and aldehyde dehydrogenese (Aldh2), were upregulated by the HFD-ED diet.

View Article: PubMed Central - PubMed

ABSTRACT

Low-grade chronic inflammatory conditions such as ageing, obesity and related metabolic disorders are associated with deterioration of skeletal muscle (SkM). Human studies have shown that marine fatty acids influence SkM function, though the underlying mechanisms of action are unknown. As a model of diet-induced obesity, we fed C57BL/6J mice either a high fat diet (HFD) with purified marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (HFD-ED), a HFD with corn oil, or normal mouse chow for 8 weeks; and used transcriptomics to identify the molecular effects of EPA and DHA on SkM. Consumption of ED-enriched HFD modulated SkM metabolism through increased gene expression of mitochondrial &beta;-oxidation and slow-fiber type genes compared with HFD-corn oil fed mice. Furthermore, HFD-ED intake increased nuclear localization of nuclear factor of activated T-cells (Nfatc4) protein, which controls fiber-type composition. This data suggests a role for EPA and DHA in mitigating some of the molecular responses due to a HFD in SkM. Overall, the results suggest that increased consumption of the marine fatty acids EPA and DHA may aid in the prevention of molecular processes that lead to muscle deterioration commonly associated with obesity-induced low-grade inflammation.

No MeSH data available.