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Dietary Flaxseed Mitigates Impaired Skeletal Muscle Regeneration: in Vivo, in Vitro and in Silico Studies

Identifieur interne : 000110 ( Main/Exploration ); précédent : 000109; suivant : 000111

Dietary Flaxseed Mitigates Impaired Skeletal Muscle Regeneration: in Vivo, in Vitro and in Silico Studies

Auteurs : Felicia Carotenuto [Italie] ; Alessandra Costa [États-Unis] ; Maria Cristina Albertini [Italie] ; Marco Bruno Luigi Rocchi [Italie] ; Alexander Rudov [Italie] ; Dario Coletti ; Marilena Minieri [Italie] ; Paolo Di Nardo [Italie] ; Laura Teodori [Italie]

Source :

RBID : Hal:hal-01294368

English descriptors

Abstract

Background: Diets enriched with n-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to exert a positive impact on muscle diseases. Flaxseed is one of the richest sources of n-3 PUFA acid α-linolenic acid (ALA). The aim of this study was to assess the effects of flaxseed and ALA in models of skeletal muscle degeneration characterized by high levels of Tumor Necrosis Factor-α (TNF). Methods: The in vivo studies were carried out on dystrophic hamsters affected by muscle damage associated with high TNF plasma levels and fed with a long-term 30% flaxseed-supplemented diet. Differentiating C2C12 myoblasts treated with TNF and challenged with ALA represented the in vitro model. Skeletal muscle morphology was scrutinized by applying the Principal Component Analysis statistical method. Apoptosis, inflammation and myogenesis were analyzed by immunofluorescence. Finally, an in silico analysis was carried out to predict the possible pathways underlying the effects of n-3 PUFAs. Results: The flaxseed-enriched diet protected the dystrophic muscle from apoptosis and preserved muscle myogenesis by increasing the myogenin and alpha myosin heavy chain. Moreover, it restored the normal expression pattern of caveolin-3 thereby allowing protein retention at the sarcolemma. ALA reduced TNF-induced apoptosis in differentiating myoblasts and prevented the TNF-induced inhibition of myogenesis, as demonstrated by the increased expression of myogenin, myosin heavy chain and caveolin-3, while promoting myotube fusion. The in silico investigation revealed that FAK pathways may play a central role in the protective effects of ALA on myogenesis. Conclusions: These findings indicate that flaxseed may exert potent beneficial effects by preserving skeletal muscle regeneration and homeostasis partly through an ALA-mediated action. Thus, dietary flaxseed and ALA may serve as a useful strategy for treating patients with muscle dystrophies.

Url:
DOI: 10.7150/ijms.13268


Affiliations:


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<org type="institution" xml:id="struct-469724" status="INCOMING">
<orgName>affiliation inconnue</orgName>
<desc>
<address>
<country key="FR"></country>
</address>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Italie</country>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.7150/ijms.13268</idno>
<series>
<title level="j">International Journal of Medical Sciences</title>
<idno type="ISSN">1449-1907</idno>
<imprint>
<date type="datePub">2016</date>
</imprint>
</series>
</biblStruct>
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<profileDesc>
<textClass>
<keywords scheme="mix" xml:lang="en">
<term>diet</term>
<term>flaxseed</term>
<term>in silico</term>
<term>inflammation</term>
<term>muscle dystrophy</term>
<term>myogenesis</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Background: Diets enriched with n-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to exert a positive impact on muscle diseases. Flaxseed is one of the richest sources of n-3 PUFA acid α-linolenic acid (ALA). The aim of this study was to assess the effects of flaxseed and ALA in models of skeletal muscle degeneration characterized by high levels of Tumor Necrosis Factor-α (TNF). Methods: The in vivo studies were carried out on dystrophic hamsters affected by muscle damage associated with high TNF plasma levels and fed with a long-term 30% flaxseed-supplemented diet. Differentiating C2C12 myoblasts treated with TNF and challenged with ALA represented the in vitro model. Skeletal muscle morphology was scrutinized by applying the Principal Component Analysis statistical method. Apoptosis, inflammation and myogenesis were analyzed by immunofluorescence. Finally, an in silico analysis was carried out to predict the possible pathways underlying the effects of n-3 PUFAs. Results: The flaxseed-enriched diet protected the dystrophic muscle from apoptosis and preserved muscle myogenesis by increasing the myogenin and alpha myosin heavy chain. Moreover, it restored the normal expression pattern of caveolin-3 thereby allowing protein retention at the sarcolemma. ALA reduced TNF-induced apoptosis in differentiating myoblasts and prevented the TNF-induced inhibition of myogenesis, as demonstrated by the increased expression of myogenin, myosin heavy chain and caveolin-3, while promoting myotube fusion. The in silico investigation revealed that FAK pathways may play a central role in the protective effects of ALA on myogenesis. Conclusions: These findings indicate that flaxseed may exert potent beneficial effects by preserving skeletal muscle regeneration and homeostasis partly through an ALA-mediated action. Thus, dietary flaxseed and ALA may serve as a useful strategy for treating patients with muscle dystrophies.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Italie</li>
<li>États-Unis</li>
</country>
<region>
<li>Pennsylvanie</li>
</region>
<settlement>
<li>Pittsburgh</li>
</settlement>
<orgName>
<li>Université de Pittsburgh</li>
</orgName>
</list>
<tree>
<noCountry>
<name sortKey="Coletti, Dario" sort="Coletti, Dario" uniqKey="Coletti D" first="Dario" last="Coletti">Dario Coletti</name>
</noCountry>
<country name="Italie">
<noRegion>
<name sortKey="Carotenuto, Felicia" sort="Carotenuto, Felicia" uniqKey="Carotenuto F" first="Felicia" last="Carotenuto">Felicia Carotenuto</name>
</noRegion>
<name sortKey="Albertini, Maria Cristina" sort="Albertini, Maria Cristina" uniqKey="Albertini M" first="Maria Cristina" last="Albertini">Maria Cristina Albertini</name>
<name sortKey="Di Nardo, Paolo" sort="Di Nardo, Paolo" uniqKey="Di Nardo P" first="Paolo" last="Di Nardo">Paolo Di Nardo</name>
<name sortKey="Minieri, Marilena" sort="Minieri, Marilena" uniqKey="Minieri M" first="Marilena" last="Minieri">Marilena Minieri</name>
<name sortKey="Rocchi, Marco Bruno Luigi" sort="Rocchi, Marco Bruno Luigi" uniqKey="Rocchi M" first="Marco Bruno Luigi" last="Rocchi">Marco Bruno Luigi Rocchi</name>
<name sortKey="Rudov, Alexander" sort="Rudov, Alexander" uniqKey="Rudov A" first="Alexander" last="Rudov">Alexander Rudov</name>
<name sortKey="Teodori, Laura" sort="Teodori, Laura" uniqKey="Teodori L" first="Laura" last="Teodori">Laura Teodori</name>
</country>
<country name="États-Unis">
<region name="Pennsylvanie">
<name sortKey="Costa, Alessandra" sort="Costa, Alessandra" uniqKey="Costa A" first="Alessandra" last="Costa">Alessandra Costa</name>
</region>
</country>
</tree>
</affiliations>
</record>

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