Funding: This work was supported, in whole or in part, by European Social Fund under the Global Grant measure Grant VP1-3.1-ŠMM-07-K-02-057 (to A.L.), European Foundation for the Study of Diabetes grant (to T.V.), NHS Grampian Endowment grant (to A.R. and S.R.G.), Kuwait Ministry of Health grant (to M.A.), Saudi Ministry of Higher Education grant (to Y.A.,) as well as Saltire scholarship, Wenner-Gren Foundation Postdoctoral Fellowship, Albert Renold Travel Fellowship and a Novo Nordisk Foundation Challenge Grant (to B.G.).Peer reviewedPublisher PD

Al-Tarrah, Mustafa

Alhindi, Yosra Zakariyya Y

Gabriel, Brendan M

Gray, Stuart R

Kilikevicius, Audrius

Lionikas, Arimantas

Ratkevicius, Aivaras

Venckunas, Tomas

PLoS ONE

English

The H55N polymorphism in the Cs gene of A/J mice has been linked to low activity of the enzyme in skeletal muscles. The aim of the study was to test this hypothesis and examine effects of low citrate synthase (CS) activity on palmitate metabolism in muscle cells. Results of the study showed that carriers of the wild type (WT) Cs (C57BL/6J and Balb/cByJ mouse strains) had higher CS activity (p < 0.01) than carriers of the A/J variant (B6.A-(rs3676616-D10Utsw1)/KjnB6 and A/J mouse strains) in the heart, liver and gastrocnemius muscle. Furthermore, the recombinant CS protein of WT showed higher CS activity than the A/J variant. In C2C12 muscle cells the shRNA mediated 47% knockdown of CS activity reduced the rate of fatty acid oxidation compared to the control cells. In summary, our results are consistent with the hypothesis that H55N substitution causes a reduction in CS activity. Furthermore, low CS activity interferes with metabolic flexibility of muscle cells

Gabriel, Brendan M,

Al-Tarrah, Mustafa,

Alhindi, Yosra,

Kilikevicius, Audrius,

Venckunas, Tomas,

Gray, Stuart R,

Lionikas, Arimantas,

Ratkevicius, Aivaras,

Lithuanian Sports University Virtual Library

H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells /

Brendan M. Gabriel

Mustafa Al-Tarrah

Yosra Alhindi

Audrius Kilikevicius

Tomas Venckunas

Stuart R. Gray

Arimantas Lionikas

Aivaras Ratkevicius

Crossref

H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells

The H55N polymorphism in the Cs gene of A/J mice has been linked to low activity of the enzyme in skeletal muscles. The aim of the study was to test this hypothesis and examine effects of low citrate synthase (CS) activity on palmitate metabolism in muscle cells. Results of the study showed that carriers of the wild type (WT) Cs (C57BL/6J and Balb/cByJ mouse strains) had higher CS activity (p &lt; 0.01) than carriers of the A/J variant (B6.A-(rs3676616-D10Utsw1)/KjnB6 and A/J mouse strains) in the heart, liver and gastrocnemius muscle. Furthermore, the recombinant CS protein of WT showed higher CS activity than the A/J variant. In C2C12 muscle cells the shRNA mediated 47% knockdown of CS activity reduced the rate of fatty acid oxidation compared to the control cells. In summary, our results are consistent with the hypothesis that H55N substitution causes a reduction in CS activity. Furthermore, low CS activity interferes with metabolic flexibility of muscle cells

Gabriel, Brendan M.

Alhindi, Yosra

Gray, Stuart R.

Enlighten

<div><p>The H55N polymorphism in the <i>Cs</i> gene of A/J mice has been linked to low activity of the enzyme in skeletal muscles. The aim of the study was to test this hypothesis and examine effects of low citrate synthase (CS) activity on palmitate metabolism in muscle cells. Results of the study showed that carriers of the wild type (WT) <i>Cs</i> (C57BL/6J and Balb/cByJ mouse strains) had higher CS activity (p < 0.01) than carriers of the A/J variant (B6.A-(rs3676616-D10Utsw1)/KjnB6 and A/J mouse strains) in the heart, liver and gastrocnemius muscle. Furthermore, the recombinant CS protein of WT showed higher CS activity than the A/J variant. In C2C12 muscle cells the shRNA mediated 47% knockdown of CS activity reduced the rate of fatty acid oxidation compared to the control cells. In summary, our results are consistent with the hypothesis that H55N substitution causes a reduction in CS activity. Furthermore, low CS activity interferes with metabolic flexibility of muscle cells.</p></div

Brendan M. Gabriel (4567807)

Mustafa Al-Tarrah (4567804)

Yosra Alhindi (4567801)

Audrius Kilikevicius (725178)

Tomas Venckunas (725180)

Stuart R. Gray (394941)

Arimantas Lionikas (394945)

Aivaras Ratkevicius (494534)

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Funding: This work was supported, in whole or in part, by European Social Fund under the Global Grant measure Grant VP1-3.1-ŠMM-07-K-02-057 (to A.L.), European Foundation for the Study of Diabetes grant (to T.V.), NHS Grampian Endowment grant (to A.R. and S.R.G.), Kuwait Ministry of Health grant (to M.A.), Saudi Ministry of Higher Education grant (to Y.A.,) as well as Saltire scholarship, Wenner-Gren Foundation Postdoctoral Fellowship, Albert Renold Travel Fellowship and a Novo Nordisk Foundation Challenge Grant (to B.G.).Peer reviewe

Aberdeen University Research

Brendan M Gabriel

Stuart R Gray

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H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells.

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http://eprints.gla.ac.uk/151042/1/151042.pdf

H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells

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