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

doi:10.1371/journal.pone.0185789

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

Medical Sciences

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

9 Downloads (Pure)

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 language	English
Article number	e0185789
Pages (from-to)	1-20
Number of pages	20
Journal	PloS ONE
Volume	12
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0185789
Publication status	Published - 2 Nov 2017

Bibliographical note

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.).

Access to Document

10.1371/journal.pone.0185789Licence: CC BY

H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells
Copyright: © 2017 Gabriel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
Final published version, 5.89 MBLicence: CC BY

Cite this

@article{156f615ae60548a6a1d8fa0440725ca6,

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

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.",

author = "Gabriel, {Brendan M} and Mustafa Al-Tarrah and Alhindi, {Yosra Zakariyya Y} and Audrius Kilikevicius and Tomas Venckunas and Gray, {Stuart R} and Arimantas Lionikas and Aivaras Ratkevicius",

note = "Funding: This work was supported, in whole or in part, by European Social Fund under the Global Grant measure Grant VP1-3.1-{\v S}MM-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.).",

year = "2017",

month = nov,

day = "2",

doi = "10.1371/journal.pone.0185789",

language = "English",

volume = "12",

pages = "1--20",

journal = "PloS ONE",

issn = "1932-6203",

publisher = "PUBLIC LIBRARY SCIENCE",

number = "11",

}

TY - JOUR

T1 - H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells

AU - Gabriel, Brendan M

AU - Al-Tarrah, Mustafa

AU - Alhindi, Yosra Zakariyya Y

AU - Kilikevicius, Audrius

AU - Venckunas, Tomas

AU - Gray, Stuart R

AU - Lionikas, Arimantas

AU - Ratkevicius, Aivaras

N1 - 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.).

PY - 2017/11/2

Y1 - 2017/11/2

N2 - 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.

AB - 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.

UR - http://europepmc.org/articles/PMC5667803

U2 - 10.1371/journal.pone.0185789

DO - 10.1371/journal.pone.0185789

M3 - Article

SN - 1932-6203

VL - 12

SP - 1

EP - 20

JO - PloS ONE

JF - PloS ONE

IS - 11

M1 - e0185789

ER -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Brendan Gabriel

Arimantas Lionikas

Cite this

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Profiles

Brendan Gabriel

Arimantas Lionikas

Cite this