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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.


Representative Western blot is shown with LaminA/C loading control. Nuclear (black bars) and cytosolic (white bars) protein extract from the gSkM of HFD-ED (left-panel) and HFD-corn oil (right-panel) were analyzed by Western blot using antibodies for total anti-Nfatc4 antibody and the cytosolic protein levels in the HFD-ED was kept to 1. Different at ** p < 0.05 and #p < 0.01.
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nutrients-08-00543-f003: Representative Western blot is shown with LaminA/C loading control. Nuclear (black bars) and cytosolic (white bars) protein extract from the gSkM of HFD-ED (left-panel) and HFD-corn oil (right-panel) were analyzed by Western blot using antibodies for total anti-Nfatc4 antibody and the cytosolic protein levels in the HFD-ED was kept to 1. Different at ** p < 0.05 and #p < 0.01.

Mentions: The calcium mediated calcineurin-Nfat signaling cascade has been suggested to upregulate slow-fiber type gene expression. Differential gene expression of gSkM from the mice fed HFD-ED compared with HFD-corn oil suggested upregulation of several Nfat (Nfatc1; Nfatc2; Nfatc4) isoforms. The slow-fiber type genes troponin C1, cardiac/slow skeletal (Tnnc1), tropomyosin 1 alpha (Tpm1) and actin alpha 1 (Actc1) complex genes and crossbridge myosin heavy polypeptide isoforms (Myh1, Myh2, Myh3, Myh6, Myh7, Myh8) were upregulated in gSkM of HFD-ED fed mice compared with HFD-corn oil animals. Protein levels of Tnnc1, a biomarker for slow muscle fiber type, were higher in gSkM of HFD-ED fed mice compared with HFD-corn oil animals (Figure 2b). Furthermore, the gene product forming complex with Nfatc2 and Nfact4, namely myogenin (Myog) and GATA Binding Protein 5 (Gata5) regulating the transcription of slow-fiber type gene expression was upregulated in the HFD-ED gSkM compared with HFD-corn oil. Nuclear localization of Nfat protein is essential for regulation of the slow-fiber-type gene expression. In the gSkM of HFD-ED fed mice, nuclear protein Nfat levels were significantly higher than HFD-corn oil fed animals (Figure 3). The master regulator of the calcineurin-Nfat signaling cascade, the regulator of calcineurin-2, Rcan2, was upregulated and its inhibitor glycogen synthase kinase 3β (Gsk3β) was downregulated in mice fed HFD-ED, compared with HFD-corn oil animals. Another transcriptional activator, suggested to be a direct target of marine fatty acids, peroxisome proliferator-activated receptor-γ coactivator 1α (Ppargc1α) was upregulated in gSkM of HFD-ED compared with HFD-corn oil fed mice.


Eicosapentaenoic and Docosahexaenoic Acid-Enriched High Fat Diet Delays Skeletal Muscle Degradation in Mice
Representative Western blot is shown with LaminA/C loading control. Nuclear (black bars) and cytosolic (white bars) protein extract from the gSkM of HFD-ED (left-panel) and HFD-corn oil (right-panel) were analyzed by Western blot using antibodies for total anti-Nfatc4 antibody and the cytosolic protein levels in the HFD-ED was kept to 1. Different at ** p < 0.05 and #p < 0.01.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037530&req=5

nutrients-08-00543-f003: Representative Western blot is shown with LaminA/C loading control. Nuclear (black bars) and cytosolic (white bars) protein extract from the gSkM of HFD-ED (left-panel) and HFD-corn oil (right-panel) were analyzed by Western blot using antibodies for total anti-Nfatc4 antibody and the cytosolic protein levels in the HFD-ED was kept to 1. Different at ** p < 0.05 and #p < 0.01.
Mentions: The calcium mediated calcineurin-Nfat signaling cascade has been suggested to upregulate slow-fiber type gene expression. Differential gene expression of gSkM from the mice fed HFD-ED compared with HFD-corn oil suggested upregulation of several Nfat (Nfatc1; Nfatc2; Nfatc4) isoforms. The slow-fiber type genes troponin C1, cardiac/slow skeletal (Tnnc1), tropomyosin 1 alpha (Tpm1) and actin alpha 1 (Actc1) complex genes and crossbridge myosin heavy polypeptide isoforms (Myh1, Myh2, Myh3, Myh6, Myh7, Myh8) were upregulated in gSkM of HFD-ED fed mice compared with HFD-corn oil animals. Protein levels of Tnnc1, a biomarker for slow muscle fiber type, were higher in gSkM of HFD-ED fed mice compared with HFD-corn oil animals (Figure 2b). Furthermore, the gene product forming complex with Nfatc2 and Nfact4, namely myogenin (Myog) and GATA Binding Protein 5 (Gata5) regulating the transcription of slow-fiber type gene expression was upregulated in the HFD-ED gSkM compared with HFD-corn oil. Nuclear localization of Nfat protein is essential for regulation of the slow-fiber-type gene expression. In the gSkM of HFD-ED fed mice, nuclear protein Nfat levels were significantly higher than HFD-corn oil fed animals (Figure 3). The master regulator of the calcineurin-Nfat signaling cascade, the regulator of calcineurin-2, Rcan2, was upregulated and its inhibitor glycogen synthase kinase 3β (Gsk3β) was downregulated in mice fed HFD-ED, compared with HFD-corn oil animals. Another transcriptional activator, suggested to be a direct target of marine fatty acids, peroxisome proliferator-activated receptor-γ coactivator 1α (Ppargc1α) was upregulated in gSkM of HFD-ED compared with HFD-corn oil fed 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 &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.