首页 » 文章 » 文章详细信息
Journal of Nutrition and Metabolism Volume 2019 ,2019-03-03
Low Citrate Synthase Activity Is Associated with Glucose Intolerance and Lipotoxicity
Research Article
Yosra Alhindi 1 Lobke M. Vaanholt 2 Mustafah Al-Tarrah 3 Stuart R. Gray 4 John R. Speakman 2 Catherine Hambly 2 Bader S. Alanazi 3 Brendan M. Gabriel 5 Arimantas Lionikas 3 Aivaras Ratkevicius 6
Show affiliations
DOI:10.1155/2019/8594825
Received 2018-08-30, accepted for publication 2019-01-12, Published 2019-01-12
PDF
摘要

Citrate synthase (CS) is a key mitochondrial enzyme. The aim of this study was to test the hypothesis that low CS activity impairs the metabolic health of mice fed a high fat diet (HFD) and promotes palmitate-induced lipotoxicity in muscle cells. C57BL/6J (B6) mice and congenic B6.A-(rs3676616-D10Utsw1)/KjnB6 (B6.A), a strain which carries the A/J allele of CS on the B6 strain background, were fed HFD (45% kcal from fat) for 12 weeks. C2C12 mouse muscle cells were used to investigate effects of CS knockdown on cell viability and signalling after incubation in 0.8 mM palmitate. CS activity, but not that of β-hydroxyacyl-coenzyme-A dehydrogenase was lower in the gastrocnemius muscle and heart of B6.A mice compared to B6 mice (P<0.001). During HFD feeding, glucose tolerance of mice decreased progressively and to a greater extent in B6.A females compared to B6 females, with males showing a similar trend. Body weight and fat gain did not differ between B6.A and B6 mice. After an 18 h incubation in 0.8 mM palmitate C2C12 muscle cells with ∼50% shRNA mediated reduction in CS activity showed lower (P<0.001) viability and increased (P<0.001) levels of cleaved caspase-3 compared to the scramble shRNA treated C2C12 cells. A/J strain variant of CS is associated with low enzyme activity and impaired metabolic health. This could be due to impaired lipid metabolism in muscle cells.

授权许可

Copyright © 2019 Yosra Alhindi et al. 2019
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

通讯作者

Yosra Alhindi.Clinical Pharmacy Department, Pharmacy Collage, Umm Al-Qura University, Makkah, Saudi Arabia, uqu.edu.sa.yzhindi@uqu.edu.sa

推荐引用方式

Yosra Alhindi,Lobke M. Vaanholt,Mustafah Al-Tarrah,Stuart R. Gray,John R. Speakman,Catherine Hambly,Bader S. Alanazi,Brendan M. Gabriel,Arimantas Lionikas,Aivaras Ratkevicius. Low Citrate Synthase Activity Is Associated with Glucose Intolerance and Lipotoxicity. Journal of Nutrition and Metabolism ,Vol.2019(2019)

您觉得这篇文章对您有帮助吗?
分享和收藏
0

是否收藏?

参考文献
[1] M. Gaster, A. C. Rustan, V. Aas, H. Beck-Nielsen. et al.(2004). Reduced lipid oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin: evidence from cultured myotubes. Diabetes.53(3):542-548. DOI: 10.1152/ajpregu.00396.2007.
[2] H. Shao, L. C. Burrage, D. S. Sinasac. (2008). Genetic architecture of complex traits: large phenotypic effects and pervasive epistasis. Proceedings of the National Academy of Sciences.105(50):19910-19914. DOI: 10.1152/ajpregu.00396.2007.
[3] R. A. Jacobs, V. Díaz, A.-K. Meinild, M. Gassmann. et al.(2013). The C57Bl/6 mouse serves as a suitable model of human skeletal muscle mitochondrial function. Experimental Physiology.98(4):908-921. DOI: 10.1152/ajpregu.00396.2007.
[4] Y. Ravussin, C. A. LeDuc, K. Watanabe, R. L. Leibel. et al.(2012). Effects of ambient temperature on adaptive thermogenesis during maintenance of reduced body weight in mice. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.303(4):R438-R448. DOI: 10.1152/ajpregu.00396.2007.
[5] R. Gherzi, M. Trabucchi, M. Ponassi, I.-E. Gallouzi. et al.(2009). Akt2-mediated phosphorylation of Pitx2 controls Ccnd1 mRNA decay during muscle cell differentiation. Cell Death and Differentiation.17(6):975-983. DOI: 10.1152/ajpregu.00396.2007.
[6] K. R. Johnson, L. H. Gagnon, C. Longo-Guess, K. L. Kane. et al.(2012). Association of a citrate synthase missense mutation with age-related hearing loss in A/J mice. Neurobiology of Aging.33(8):1720-1729. DOI: 10.1152/ajpregu.00396.2007.
[7] J. R. Speakman. (2013). Measuring energy metabolism in the mouse-theoretical, practical, and analytical considerations. Frontiers in Physiology.4:34. DOI: 10.1152/ajpregu.00396.2007.
[8] C. Martin-Granados, A. Philp, S. K. Oxenham, A. R. Prescott. et al.(2008). Depletion of protein phosphatase 4 in human cells reveals essential roles in centrosome maturation, cell migration and the regulation of Rho GTPases. The International Journal of Biochemistry and Cell Biology.40(10):2315-2332. DOI: 10.1152/ajpregu.00396.2007.
[9] A. Ratkevicius, A. M. Carroll, A. Kilikevicius. (2010). H55N polymorphism as a likely cause of variation in citrate synthase activity of mouse skeletal muscle. Physiological Genomics.42A(2):96-102. DOI: 10.1152/ajpregu.00396.2007.
[10] A. Kilikevicius, T. Venckunas, R. Zelniene. (2013). Divergent physiological characteristics and responses to endurance training among inbred mouse strains. Scandinavian Journal of Medicine and Science in Sports.23(5):657-668. DOI: 10.1152/ajpregu.00396.2007.
[11] K. I. Watt, R. T. Jaspers, P. Atherton. (2010). SB431542 treatment promotes the hypertrophy of skeletal muscle fibers but decreases specific force. Muscle and Nerve.41(5):624-629. DOI: 10.1152/ajpregu.00396.2007.
[12] D. K. Choi, T. S. Oh, J.-W. Choi. (2011). Gender difference in proteome of brown adipose tissues between male and female rats exposed to a high fat diet. Cellular Physiology and Biochemistry.28(5):933-948. DOI: 10.1152/ajpregu.00396.2007.
[13] G. E. Truett, P. Heeger, R. L. Mynatt, A. A. Truett. et al.(2000). Preparation of PCR-quality mouse genomic DNA with hot sodium hydroxide and tris (HotSHOT). Biotechniques.29(1):52-54. DOI: 10.1152/ajpregu.00396.2007.
[14] D.-H. Han, C. R. Hancock, S. R. Jung, K. Higashida. et al.(2011). Deficiency of the mitochondrial electron transport chain in muscle does not cause insulin resistance. PLoS One.6(5). DOI: 10.1152/ajpregu.00396.2007.
[15] W. T. Friedewald, R. I. Levy, D. S. Fredrickson. (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical Chemistry.18(6):499-502. DOI: 10.1152/ajpregu.00396.2007.
[16] C. R. Hancock, D.-H. Han, M. Chen. (2008). High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proceedings of the National Academy of Sciences.105(22):7815-7820. DOI: 10.1152/ajpregu.00396.2007.
[17] C. Henique, A. Mansouri, G. Fumey. (2010). Increased mitochondrial fatty acid oxidation is sufficient to protect skeletal muscle cells from palmitate-induced apoptosis. Journal of Biological Chemistry.285(47):36818-36827. DOI: 10.1152/ajpregu.00396.2007.
[18] M. Capková, J. Houstek, H. Hansíková, V. Hainer. et al.(2002). Activities of cytochrome c oxidase and citrate synthase in lymphocytes of obese and normal-weight subjects. International Journal of Obesity.26(8):1110-1117. DOI: 10.1152/ajpregu.00396.2007.
[19] L. C. Burrage, A. E. Baskin-Hill, D. S. Sinasac. (2010). Genetic resistance to diet-induced obesity in chromosome substitution strains of mice. Mammalian Genome.21(3-4):115-129. DOI: 10.1152/ajpregu.00396.2007.
[20] C. C. Lin, T. L. Cheng, W. H. Tsai. (2012). Loss of the respiratory enzyme citrate synthase directly links the Warburg effect to tumor malignancy. Scientific Reports.2(1):785. DOI: 10.1152/ajpregu.00396.2007.
[21] N. Ørtenblad, M. Mogensen, I. Petersen. (2005). Reduced insulin-mediated citrate synthase activity in cultured skeletal muscle cells from patients with type 2 diabetes: evidence for an intrinsic oxidative enzyme defect. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.1741(1-2):206-214. DOI: 10.1152/ajpregu.00396.2007.
[22] S. F. Leibowitz, J. Alexander, J. T. Dourmashkin, J. O. Hill. et al.(2005). Phenotypic profile of SWR/J and A/J mice compared to control strains: possible mechanisms underlying resistance to obesity on a high-fat diet. Brain Research.1047(2):137-147. DOI: 10.1152/ajpregu.00396.2007.
[23] J. A. Houmard. (2008). Intramuscular lipid oxidation and obesity. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.294(4):R1111-R1116. DOI: 10.1152/ajpregu.00396.2007.
[24] V. Kus, T. Prazak, P. Brauner. (2008). Induction of muscle thermogenesis by high-fat diet in mice: association with obesity-resistance. American Journal of Physiology-Endocrinology and Metabolism.295(2):E356-E367. DOI: 10.1152/ajpregu.00396.2007.
[25] J. B. Singer, A. E. Hill, L. C. Burrage. (2004). Genetic dissection of complex traits with chromosome substitution strains of mice. Science.304(5669):445-448. DOI: 10.1152/ajpregu.00396.2007.
[26] B. M. Gabriel, M. Al-Tarrah, Y. Alhindi. (2017). H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells. PLoS One.12(11). DOI: 10.1152/ajpregu.00396.2007.
[27] G. S. Hotamisligil. (2006). Inflammation and metabolic disorders. Nature.444(7121):860-867. DOI: 10.1152/ajpregu.00396.2007.
[28] S. Larsen, J. Nielsen, C. N. Hansen. (2012). Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. Journal of Physiology.590(14):3349-3360. DOI: 10.1152/ajpregu.00396.2007.
[29] C. Hambly, A. Adams, J.-M. Fustin, K. A. Rance. et al.(2012). Mice with low metabolic rates are not susceptible to weight gain when fed a high-fat diet. Obesity Research.13(3):556-566. DOI: 10.1152/ajpregu.00396.2007.
[30] S. K. Powers, M. P. Wiggs, J. A. Duarte, A. M. Zergeroglu. et al.(2012). Mitochondrial signaling contributes to disuse muscle atrophy. American Journal of Physiology-Endocrinology and Metabolism.303(1):E31-E39. DOI: 10.1152/ajpregu.00396.2007.
[31] J. M. Kristensen, V. Skov, S. J. Petersson. (2014). A PGC-1- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance. Diabetologia.57(5):1006-1015. DOI: 10.1152/ajpregu.00396.2007.
[32] J. B. d. V. Weir. (1949). New methods for calculating metabolic rate with special reference to protein metabolism. Journal of Physiology.109(1-2):1-9. DOI: 10.1152/ajpregu.00396.2007.
[33] S. J. Lessard, D. A. Rivas, E. J. Stephenson. (2011). Exercise training reverses impaired skeletal muscle metabolism induced by artificial selection for low aerobic capacity. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.300(1):R175-R182. DOI: 10.1152/ajpregu.00396.2007.
[34] J. R. Speakman, E. Król. (2005). Comparison of different approaches for the calculation of energy expenditure using doubly labeled water in a small mammal. Physiological and Biochemical Zoology.78(4):650-667. DOI: 10.1152/ajpregu.00396.2007.
[35] U. S. Pettersson, T. B. Waldén, P.-O. Carlsson, L. Jansson. et al.(2012). Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory T cell population in adipose tissue. PLoS One.7(9):e46057. DOI: 10.1152/ajpregu.00396.2007.
[36] G. J. Cooney, A. L. Thompson, S. M. Furler, J. Ye. et al.(2002). Muscle long-chain acyl CoA esters and insulin resistance. Annals of the New York Academy of Sciences.967(1):196-207. DOI: 10.1152/ajpregu.00396.2007.
[37] X. Han, R. Ge, G. Xie. (2015). Caspase-mediated apoptosis in the cochleae contributes to the early onset of hearing loss in A/J mice. ASN Neuro.7(1). DOI: 10.1152/ajpregu.00396.2007.
[38] S.-H. Wu, L.-N. Zhang, J. R. Speakman, D.-H. Wang. et al.(2009). Limits to sustained energy intake. XI. A test of the heat dissipation limitation hypothesis in lactating Brandt’s voles (). Journal of Experimental Biology.212(21):3455-3465. DOI: 10.1152/ajpregu.00396.2007.
[39] D.-H. Han, C. Hancock, S.-R. Jung, J. O. Holloszy. et al.(2009). Is “fat-induced” muscle insulin resistance rapidly reversible?. American Journal of Physiology-Endocrinology and Metabolism.297(1):E236-E241. DOI: 10.1152/ajpregu.00396.2007.
文献评价指标
浏览 58次
下载全文 7次
评分次数 0次
用户评分 0.0分
分享 0次