Hostname: page-component-8448b6f56d-t5pn6 Total loading time: 0 Render date: 2024-04-24T19:16:23.364Z Has data issue: false hasContentIssue false

Effects of Creatine and Exercise on Skeletal Muscle of FRG1-Transgenic Mice

Published online by Cambridge University Press:  02 December 2014

Daniel I. Ogborn
Affiliation:
Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada
Katelyn J. Smith
Affiliation:
Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada
Justin D. Crane
Affiliation:
Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada
Adeel Safdar
Affiliation:
Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada
Bart P. Hettinga
Affiliation:
Department of Pediatrics and Medicine, McMaster University, Hamilton, Ontario, Canada
Rossella Tupler
Affiliation:
Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
Mark A. Tarnopolsky*
Affiliation:
Department of Pediatrics and Medicine, McMaster University, Hamilton, Ontario, Canada
*
McMaster University Medical Centre, RM 2H26, 1200 Main St West, Hamilton, Ontario, L8N 3Z5, Canada.
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background:

The FRG1-transgenic mouse displays muscle dysfunction and atrophy reminiscent of fascioscapulohumeral muscular dystrophy (FSHD) and could provide a model to determine potential therapeutic interventions.

Methods:

To determine if FRG1 mice benefit from treatments that improve muscle mass and function, mice were treated with creatine alone (Cr) or in combination with treadmill exercise (CrEX).

Results:

The CrEx treatment increased quadriceps weight, mitochondrial content (cytochome c oxidase (COX) activity, COX subunit one and four protein), and induced greater improvements in grip strength and rotarod fall speed. While Cr increased COX subunits one and four protein, no effect on muscle mass or performance was found. Since Cr resulted in no functional improvements, the benefits of CrEx may be mediated by exercise; however, the potential synergistic action of the combined treatment cannot be excluded.

Conclusion:

Treatment with CrEx attenuates atrophy and muscle dysfunction associated with FRG1 overexpression. These data suggest exercise and creatine supplementation may benefit individuals with FSHD.

Type
Research Article
Copyright
Copyright © The Canadian Journal of Neurological 2012

References

1Tawil, R, Van Der Maarel, SM.Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2006 Jul;34(1):115.Google Scholar
2McCartney, N, Moroz, D, Garner, SH, McComas, AJ.The effects of strength training in patients with selected neuromuscular disorders. Med Sci Sports Exerc. 1988 Aug;20(4):3628.Google Scholar
3van der Kooi, EL, Kalkman, JS, Lindeman, E, et al.Effects of training and albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy. J Neurol. 2007 Jul;254(7):93140.Google Scholar
4van der Kooi, EL, Lindeman, E, Riphagen, I.Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2005(1):CD003907.Google Scholar
5van der Kooi, EL, Vogels, OJ, van Asseldonk, RJ, et al.Strength training and albuterol in facioscapulohumeral muscular dystrophy. Neurology. 2004 Aug 24;63(4): 7028.Google Scholar
6Banerjee, B, Sharma, U, Balasubramanian, K, Kalaivani, M, Kalra, V, Jagannathan, NR.Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized, placebo-controlled 31P MRS study. Magn Reson Imaging. 2010 Jun;28(5):698707.Google Scholar
7Kley, RA, Vorgerd, M, Tarnopolsky, MA.Creatine for treating muscle disorders. Cochrane Database Syst Rev. 2007(1):CD004760.Google Scholar
8Tarnopolsky, MA.Clinical use of creatine in neuromuscular and neurometabolic disorders. Subcell Biochem. 2007;46:183204.Google Scholar
9Tarnopolsky, M, Martin, J.Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology. 1999 Mar 10;52(4): 8547.Google Scholar
10Louis, M, Lebacq, J, Poortmans, JR, et al.Beneficial effects of creatine supplementation in dystrophic patients. Muscle Nerve. 2003 May;27(5):60410.Google Scholar
11Kley, RA, Tarnopolsky, MA, Vorgerd, M.Creatine treatment in muscle disorders: a meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):3667.Google Scholar
12Louis, M, Raymackers, JM, Debaix, H, Lebacq, J, Francaux, M.Effect of creatine supplementation on skeletal muscle of mdx mice. Muscle Nerve. 2004 May;29(5):68792.Google Scholar
13Passaquin, AC, Renard, M, Kay, L, et al.Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice. Neuromuscul Disord. 2002 Feb;12(2):17482.Google Scholar
14Pulido, SM, Passaquin, AC, Leijendekker, WJ, Challet, C, Wallimann, T, Ruegg, UT.Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells. FEBS Lett. 1998 Nov 20;439(3): 35762.Google Scholar
15Tarnopolsky, MA, Mahoney, DJ, Vajsar, J, et al.Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy. Neurology. 2004 May 25;62(10): 17717.Google Scholar
16Tarnopolsky, M, Mahoney, D, Thompson, T, Naylor, H, Doherty, TJ.Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. Muscle Nerve. 2004 Jan;29(1):518.Google Scholar
17Walter, MC, Reilich, P, Lochmuller, H, et al.Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. J Neurol. 2002 Dec;249(12):171722.Google Scholar
18Kaczor, JJ, Hall, JE, Payne, E, Tarnopolsky, MA.Low intensity training decreases markers of oxidative stress in skeletal muscle of mdx mice. Free Radic Biol Med. 2007 Jul 1;43(1): 14554.Google Scholar
19Landisch, RM, Kosir, AM, Nelson, SA, Baltgalvis, KA, Lowe, DA.Adaptive and nonadaptive responses to voluntary wheel running by mdx mice. Muscle Nerve. 2008 Oct;38(4):1290303.Google Scholar
20Gabellini, D, D’Antona, G, Moggio, M, et al.Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1. Nature. 2006 Feb 23;439(7079): 9737.Google Scholar
21Olsen, DB, Orngreen, MC, Vissing, J.Aerobic training improves exercise performance in facioscapulohumeral muscular dystrophy. Neurology. 2005 Mar 22;64(6): 10646.Google Scholar
22D’Antona, G, Brocca, L, Pansarasa, O, Rinaldi, C, Tupler, R, Bottinelli, R.Structural and functional alterations of muscle fibres in the novel mouse model of facioscapulohumeral muscular dystrophy. J Physiol. 2007 Nov 1;584(Pt 3):9971009.CrossRefGoogle Scholar
23Parise, G, Brose, AN, Tarnopolsky, MA.Resistance exercise training decreases oxidative damage to DNA and increases cytochrome oxidase activity in older adults. Exp Gerontol. 2005 Mar;40(3):17380.Google Scholar
24Boveris, A, Navarro, A.Systemic and mitochondrial adaptive responses to moderate exercise in rodents. Free Radic Biol Med. 2008 Jan 15;44(2): 2249.Google Scholar
25Hall, JE, Kaczor, JJ, Hettinga, BP, Isfort, RJ, Tarnopolsky, MA.Effects of a CRF2R agonist and exercise on mdx and wildtype skeletal muscle. Muscle Nerve. 2007 Sep;36(3):33641.Google Scholar
26Wineinger, MA, Abresch, RT, Walsh, SA, Carter, GT.Effects of aging and voluntary exercise on the function of dystrophic muscle from mdx mice. Am J Phys Med Rehabil. 1998 Jan-Feb;77(1):207.Google Scholar
27Voet, NB, Bleijenberg, G, Padberg, GW, van Engelen, BG, Geurts, AC.Effect of aerobic exercise training and cognitive behavioural therapy on reduction of chronic fatigue in patients with facioscapulohumeral dystrophy: protocol of the FACTS-2-FSHD trial. BMC Neurol. 2010;10:56.Google Scholar
28Coggan, AR, Spina, RJ, King, DS, et al.Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women. J Appl Physiol. 1992 May;72(5):17806.Google Scholar
29Orngreen, MC, Olsen, DB, Vissing, J.Aerobic training in patients with myotonic dystrophy type 1. Ann Neurol. 2005 May;57(5):7547.Google Scholar
30Harber, MP, Konopka, AR, Douglass, MD, et al.Aerobic exercise training improves whole muscle and single myofiber size and function in older women. Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R14529.Google Scholar
31Winokur, ST, Chen, YW, Masny, PS, et al.Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation. Hum Mol Genet. 2003 Nov 15;12(22): 2895907.Google Scholar
32Slipetz, DM, Aprille, JR, Goodyer, PR, Rozen, R.Deficiency of complex III of the mitochondrial respiratory chain in a patient with facioscapulohumeral disease. Am J Hum Genet. 1991 Mar;48(3):50210.Google Scholar
33Munsat, TL, Piper, D, Cancilla, P, Mednick, J.Inflammatory myopathy with facioscapulohumeral distribution. Neurology. 1972 Apr;22(4):33547.Google Scholar
34Casey, A, Constantin-Teodosiu, D, Howell, S, Hultman, E, Greenhaff, PL.Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol. 1996 Jul;271(1 Pt 1):E317.Google Scholar
35Harris, RC, Soderlund, K, Hultman, E.Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond). 1992 Sep;83(3):36774.CrossRefGoogle ScholarPubMed
36Hultman, E, Soderlund, K, Timmons, JA, Cederblad, G, Greenhaff, PL.Muscle creatine loading in men. J Appl Physiol. 1996 Jul;81(1):2327.Google Scholar
37Parise, G, Mihic, S, MacLennan, D, Yarasheski, KE, Tarnopolsky, MA.Effects of acute creatine monohydrate supplementation on leucine kinetics and mixed-muscle protein synthesis. J Appl Physiol. 2001 Sep;91(3):10417.Google Scholar
38Smith, SA, Montain, SJ, Zientara, GP, Fielding, RA.Use of phosphocreatine kinetics to determine the influence of creatine on muscle mitochondrial respiration: an in vivo 31P-MRS study of oral creatine ingestion. J Appl Physiol. 2004 Jun;96(6):228892.Google Scholar
39Walsh, B, Tiivel, T, Tonkonogi, M, Sahlin, K.Increased concentrations of P(i) and lactic acid reduce creatine-stimulated respiration in muscle fibers. J Appl Physiol. 2002 Jun;92(6):22736.Google Scholar
40Walsh, B, Tonkonogi, M, Soderlund, K, Hultman, E, Saks, V, Sahlin, K.The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle. J Physiol. 2001 Dec 15;537(Pt 3):9718.Google Scholar
41Cunningham, JT, Rodgers, JT, Arlow, DH, Vazquez, F, Mootha, VK, Puigserver, P.mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature. 2007 Nov 29;450(7170): 73640.Google Scholar
42Gough, DJ, Corlett, A, Schlessinger, K, Wegrzyn, J, Larner, AC, Levy, DE.Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science. 2009 Jun 26;324(5935): 17136.Google Scholar
43Wegrzyn, J, Potla, R, Chwae, YJ, et al.Function of mitochondrial Stat3 in cellular respiration. Science. 2009 Feb 6;323(5915): 7937.Google Scholar
44Yokogami, K, Wakisaka, S, Avruch, J, Reeves, SA.Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR. Curr Biol. 2000 Jan 13;10(1): 4750.Google Scholar
45Kutz, MR, Gunter, MJ.Creatine monohydrate supplementation on body weight and percent body fat. J Strength Cond Res. 2003 Nov;17(4):81721.Google Scholar
46Safdar, A, Yardley, NJ, Snow, R, Melov, S, Tarnopolsky, MA.Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol Genomics. 2008 Jan 17;32(2): 21928.Google Scholar
47Ziegenfuss, TN, Lowery, LM, Lemon, PW.Acute fluid volume changes in men during three days of creatine supplementation. J Exerc Physiol. 1998;1(3).Google Scholar
48Vandenburgh, HH, Hatfaludy, S, Karlisch, P, Shansky, J.Skeletal muscle growth is stimulated by intermittent stretch-relaxation in tissue culture. Am J Physiol. 1989 Mar;256(3 Pt 1):C67482.Google Scholar