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

Gabriel, B. M., Al-Tarrah, M., Alhindi, Y., Kilikevicius, A., Venckunas, T., Gray, S. R. , Lionikas, A. and Ratkevicius, A. (2017) H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells. PLoS ONE, 12(11), e0185789. (doi: 10.1371/journal.pone.0185789) (PMID:29095821) (PMCID:PMC5667803)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gray, Professor Stuart
• Authors: Gabriel, B. M., Al-Tarrah, M., Alhindi, Y., Kilikevicius, A., Venckunas, T., Gray, S. R., Lionikas, A., and Ratkevicius, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © 2017 Gabriel et al.
• First Published: First published in PLoS ONE 12(11): e0185789
• Publisher Policy: Reproduced under a Creative Commons License