Abstract
| Original language | English |
|---|---|
| Article number | e0185789 |
| Pages (from-to) | 1-20 |
| Number of pages | 20 |
| Journal | PloS ONE |
| Volume | 12 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2 Nov 2017 |
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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 journal › Article
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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.
U2 - 10.1371/journal.pone.0185789
DO - 10.1371/journal.pone.0185789
M3 - Article
VL - 12
SP - 1
EP - 20
JO - PloS ONE
JF - PloS ONE
SN - 1932-6203
IS - 11
M1 - e0185789
ER -