Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of GSK-3 Activity

Intramuscular fat is important in large animal livestock species in regard to meat quality and in humans is of clinical significance in particular in relation to insulin resistance. The canonical Wnt signalling pathway has been implicated at a whole body level in regulating relative levels of adipos...

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Main Authors: Zoe Redshaw, Paul Thomas Loughna
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-06-01
Series:Frontiers in Veterinary Science
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fvets.2018.00110/full
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author Zoe Redshaw
Zoe Redshaw
Paul Thomas Loughna
author_facet Zoe Redshaw
Zoe Redshaw
Paul Thomas Loughna
author_sort Zoe Redshaw
collection DOAJ
description Intramuscular fat is important in large animal livestock species in regard to meat quality and in humans is of clinical significance in particular in relation to insulin resistance. The canonical Wnt signalling pathway has been implicated at a whole body level in regulating relative levels of adiposity versus lean body mass. Previously we have shown that pig muscle cells can undergo adipogenic differentiation to a degree that is dependent upon the specific muscle source. In this work we examine the role of the canonical Wnt pathway which acts through inactivation of glycogen synthase kinase-3 (GSK-3) in the regulation of adipogenic differentiation in muscle cells derived from the pig semimembranosus muscle.The application of lithium chloride to muscle derived cells significantly increased the phosphorylation of GSK-3β and thus inhibited its activity thus mimicking Wnt signaling. This was associated with a significant decrease in the expression of the adipogenic transcription factor PPARγ and an almost complete inhibition of adipogenesis in the cells. The data also suggest that GSK-3α plays, at most, a small role in this process.Studies in vivo have suggested that the Wnt pathway is a major regulator of whole body adiposity. In this study we have shown that the ability of cells derived from porcine skeletal muscle to differentiate along an adipogenic lineage, in vitro, is severely impaired by mimicking the action of this pathway. This was done by inactivation of GSK-3β by the use of Lithium Chloride.
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spelling doaj.art-0b993f0be58841bca141bb31943165042022-12-22T01:48:40ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692018-06-01510.3389/fvets.2018.00110267297Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of GSK-3 ActivityZoe RedshawZoe RedshawPaul Thomas LoughnaIntramuscular fat is important in large animal livestock species in regard to meat quality and in humans is of clinical significance in particular in relation to insulin resistance. The canonical Wnt signalling pathway has been implicated at a whole body level in regulating relative levels of adiposity versus lean body mass. Previously we have shown that pig muscle cells can undergo adipogenic differentiation to a degree that is dependent upon the specific muscle source. In this work we examine the role of the canonical Wnt pathway which acts through inactivation of glycogen synthase kinase-3 (GSK-3) in the regulation of adipogenic differentiation in muscle cells derived from the pig semimembranosus muscle.The application of lithium chloride to muscle derived cells significantly increased the phosphorylation of GSK-3β and thus inhibited its activity thus mimicking Wnt signaling. This was associated with a significant decrease in the expression of the adipogenic transcription factor PPARγ and an almost complete inhibition of adipogenesis in the cells. The data also suggest that GSK-3α plays, at most, a small role in this process.Studies in vivo have suggested that the Wnt pathway is a major regulator of whole body adiposity. In this study we have shown that the ability of cells derived from porcine skeletal muscle to differentiate along an adipogenic lineage, in vitro, is severely impaired by mimicking the action of this pathway. This was done by inactivation of GSK-3β by the use of Lithium Chloride.https://www.frontiersin.org/article/10.3389/fvets.2018.00110/fullWntskeletal muscleGSK-3βPPARγadipogenesis
spellingShingle Zoe Redshaw
Zoe Redshaw
Paul Thomas Loughna
Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of GSK-3 Activity
Frontiers in Veterinary Science
Wnt
skeletal muscle
GSK-3β
PPARγ
adipogenesis
title Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of GSK-3 Activity
title_full Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of GSK-3 Activity
title_fullStr Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of GSK-3 Activity
title_full_unstemmed Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of GSK-3 Activity
title_short Adipogenic Differentiation of Muscle Derived Cells is Repressed by Inhibition of GSK-3 Activity
title_sort adipogenic differentiation of muscle derived cells is repressed by inhibition of gsk 3 activity
topic Wnt
skeletal muscle
GSK-3β
PPARγ
adipogenesis
url https://www.frontiersin.org/article/10.3389/fvets.2018.00110/full
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AT zoeredshaw adipogenicdifferentiationofmusclederivedcellsisrepressedbyinhibitionofgsk3activity
AT paulthomasloughna adipogenicdifferentiationofmusclederivedcellsisrepressedbyinhibitionofgsk3activity