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

PloS One
Brendan M GabrielA Ratkevicius

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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Citations

Jan 17, 2019·Medicine and Science in Sports and Exercise·Huayu ShangRuiyuan Wang
Jan 13, 2021·Physiological Reports·Iris Prunonosa CerveraNicholas M Morton
Jul 13, 2021·Experimental Gerontology·Mindaugas KvedarasAivaras Ratkevicius

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Methods Mentioned

BETA
genotyping
PCR
FCS
Assay
biopsies

Software Mentioned

LightCycler ® 480
Universal Probe library
ImageJ

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