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

Brendan M Gabriel, Mustafa Al-Tarrah, Yosra Zakariyya Y Alhindi, Audrius Kilikevicius, Tomas Venckunas, Stuart R Gray, Arimantas Lionikas, Aivaras Ratkevicius

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Abstract

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.
Original languageEnglish
Article numbere0185789
Pages (from-to)1-20
Number of pages20
JournalPloS ONE
Volume12
Issue number11
DOIs
Publication statusPublished - 2 Nov 2017

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Citrate (si)-Synthase
citrate (si)-synthase
Polymorphism
Lipid Metabolism
lipid metabolism
myocytes
Muscle Cells
Muscle
Cells
genetic polymorphism
mice
Skeletal Muscle
beta oxidation
Palmitates
palmitates
Metabolism
Liver
Small Interfering RNA
skeletal muscle
Myocardium

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Gabriel, B. M., Al-Tarrah, M., Alhindi, Y. Z. Y., Kilikevicius, A., Venckunas, T., Gray, S. R., ... Ratkevicius, A. (2017). H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells. PloS ONE, 12(11), 1-20. [e0185789]. https://doi.org/10.1371/journal.pone.0185789

H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells. / Gabriel, Brendan M; Al-Tarrah, Mustafa; Alhindi, Yosra Zakariyya Y; Kilikevicius, Audrius; Venckunas, Tomas; Gray, Stuart R; Lionikas, Arimantas; Ratkevicius, Aivaras.

In: PloS ONE, Vol. 12, No. 11, e0185789, 02.11.2017, p. 1-20.

Research output: Contribution to journalArticle

Gabriel, BM, Al-Tarrah, M, Alhindi, YZY, Kilikevicius, A, Venckunas, T, Gray, SR, Lionikas, A & Ratkevicius, A 2017, 'H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells', PloS ONE, vol. 12, no. 11, e0185789, pp. 1-20. https://doi.org/10.1371/journal.pone.0185789
Gabriel BM, Al-Tarrah M, Alhindi YZY, Kilikevicius A, Venckunas T, Gray SR et al. H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells. PloS ONE. 2017 Nov 2;12(11):1-20. e0185789. https://doi.org/10.1371/journal.pone.0185789
Gabriel, Brendan M ; Al-Tarrah, Mustafa ; Alhindi, Yosra Zakariyya Y ; Kilikevicius, Audrius ; Venckunas, Tomas ; Gray, Stuart R ; Lionikas, Arimantas ; Ratkevicius, Aivaras. / H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells. In: PloS ONE. 2017 ; Vol. 12, No. 11. pp. 1-20.
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abstract = "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.",
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