NMR-based metabolomic analysis for the effects of creatine supplementation on mouse myoblast cell line C2C12

Wenqi Xu, Donghai Lin, and Caihua Huang

The Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China

Acta Biochim Biophys Sin 2017, 49: 617–627; doi: 10.1093/abbs/gmx043

Creatine (Cr) supplementation has drawn much attention from researchers owing to its widespread efficacy in sports, and more recently, in therapeutic fields. However, the underlying molecular mechanisms remain elusive. Here, we performed nuclear magnetic resonance-based metabolomic analysis to address the metabolic profile of aqueous extracts from the mouse myoblast cell line C2C12 exposed to 2 mM Cr for 24 h (the Cr-treated group). Results showed that Cr supplementation facilitated the proliferation of C2C12 myoblasts. Both pattern recognition and hierarchical cluster analyses demonstrated that the metabolic profiles of the Cr-treated and control groups were distinctly different. We identified 13 characteristic metabolites significantly responsible for the discrimination of metabolic profiles between the two groups, through orthogonal projection to latent structures discriminant analysis and independent samples t-test. We further verified the discrimination performances of these metabolites by conducting univariate receiver operating characteristic curve analysis. Compared with the control group, the Cr-treated group exhibited increased levels of Cr, phosphocreatine (PCr), glutathione (GSH), and glucose, but decreased levels of leucine, valine, isoleucine, phenylalanine, methionine, choline, O-phosphocholine, sn-glycero-3-phosphocholine, and glycerol. Our results demonstrated that Cr supplementation upregulated PCr and glucose, promoted trichloroacetic acid cycle anaplerotic flux and GSH-mediated antioxidant capacity, and stabilized lipid membranes through suppressing glycerophospholipid metabolism. Our work provides new clues to the molecular mechanisms underlying the pleiotropic effects of Cr in muscle cells.

Metabolic profiles between the control and Cr-treated groups

阅读原文: http://www.abbs.org.cn/arts.asp?id=4177

获取全文: abbs@sibs.ac.cn

相关论文:

1 The potential therapeutic effects of creatine supplementation on body composition and muscle function in cancer

2 Creatine and creatinine metabolism

3 Long-term creatine intake is beneficial to muscle performance during resistance training

4 Impaired muscle uptake of creatine in spinal and bulbar muscular atrophy

5 Beyond muscles: The untapped potential of creatine

6 Muscle creatine loading in men

7 Isolated heart muscle of creatine kinase deficient mice is unable to maintain high-performance states and present altered myocardial calcium homeostasis

8 Myocyte-specific expression of the sarcomeric mitochondrial creatine kinase gene in heart and skeletal muscle