PGC-1α: important for exercise performance?
2008; American Physiological Society; Volume: 104; Issue: 5 Linguagem: Catalão
10.1152/japplphysiol.90346.2008
ISSN8750-7587
AutoresHenriette Pilegaard, Erik A. Richter,
Tópico(s)Mitochondrial Function and Pathology
ResumoINVITED EDITORIALPGC-1α: important for exercise performance?Henriette Pilegaard, and Erik A. RichterHenriette Pilegaard, and Erik A. RichterPublished Online:01 May 2008https://doi.org/10.1152/japplphysiol.90346.2008MoreSectionsPDF (55 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat since the identification of the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α as a factor interacting with PPARγ in brown adipose tissue (BAT) (12), it has become clear that PGC-1α plays important roles in regulating several cellular processes in many different tissues (10), including mitochondrial biogenesis in skeletal muscle (1, 9).Previously, muscle-specific overexpression of PGC-1α resulted in the conversion of otherwise “white” glycolytic muscle to “red” oxidative muscle with a dramatic upregulation of typical oxidative genes/proteins like cytochrome c and cytochrome oxidase (9). These compelling findings indicated that simply overexpressing PGC-1α results in muscle characteristics usually found in highly endurance-trained muscle. It was in fact proposed that induction of PGC-1α might be used as “an exercise pill” providing the beneficial effects of exercise training without having to leave the couch (1a, 15). The importance of PGC-1α in regulating mitochondrial biogenesis in skeletal muscle has further been underlined by the reduced expression of genes/proteins involved in oxidative metabolism in skeletal muscle of both whole body and muscle-specific PGC-1α knockout mice (1, 4, 8). Moreover, the physiological impact of these modifications in skeletal muscle has consistently been reported by reduced exercise capacity of both whole body and muscle-specific PGC-1α knockout mice (4, 8).In their article in the Journal of Applied Physiology, Calvo et al. (3) address the effects of increased muscle PGC-1α levels on exercise performance. Mice with muscle-specific overexpression of PGC-1α (MCK-PGC-1α) demonstrated marked improvements in exercise performance both during submaximal exercise intensities and during graded exercise to exhaustion. Intriguingly, the MCK-PGC-1α mice exhibited lower respiratory exchange ratio (RER) values during submaximal as well as maximal exercise intensities, reflecting that the molecular modifications induced by high PGC-1α levels increase fat oxidation and thus likely provide a carbohydrate-sparing effect relative to wild-type mice. Interestingly, at maximal exercise the RER value was below 1 in the MCK-PGC-1α mice, suggesting that no major metabolism/lactic acid-induced hyperventilation occurred.The study by Calvo et al (3) also presents mRNA data on genes encoding enzymes in oxidative metabolism, supporting previous findings (9), but also specifically increased mRNA levels of fat metabolism genes, suggesting an increased capacity for fat metabolism, which is supported by an increased fat oxidation during exercise in these mice.The MCK PGC-1α mice also exhibited ∼20% higher peak oxygen uptake than wild-type mice (3). This finding may seem surprising as the general opinion appears to be that whole body peak oxygen uptake at least in humans is limited by the pump capacity of the heart (13). However, despite possible species differences, the MCK-PGC-1α mice do have slightly elevated PGC-1α mRNA levels in the heart, and it may thus be speculated that this is sufficient to elicit the observed effects on peak oxygen uptake, although additional experiments are needed to clarify this. Of note, on the other hand, is also that very high levels of PGC-1α in the mouse heart will result in cardiomyopathy (7).Together these findings show that PGC-1α-induced changes in metabolic protein expression profile can indeed change performance and metabolism during exercise in mice. This strongly supports that PGC-1α can be a key factor in regulating adaptive responses to regular endurance exercise, leading to enhanced oxidative capacity of skeletal muscle and thus increased capacity for both fat and carbohydrate utilization. As a single exercise bout elicits a transient increase in PGC-1α gene expression (2, 11) and AMPK has been shown to phosphorylate and activate PGC-1α (6), such exercise-induced regulation could be through both exercise-induced PGC-1α expression and AMPK-mediated PGC-1α activation (5). However, a previous study has suggested that skeletal muscle-specific PGC-1α overexpression can be associated with reduced exercise performance during high-intensity exercise, perhaps due to inability to utilize muscle glycogen (14), and PGC-1α knockout mice do in fact have the ability to increase the expression of mitochondrial proteins with training (8). Thus the actual physiological role of PGC-1α expression/activation in skeletal muscle in response to exercise still needs to be more carefully established.REFERENCES1 Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS, Spiegelman BM. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab 1: 259–271, 2005.Crossref | PubMed | ISI | Google Scholar1a Associated Press. Exercise pill is possible. Wired ( www.wired.com/medtech/health/news/2002/04/51729).Google Scholar2 Baar K, Wende AR, Jones TE, Marison M, Nolte LA, Chen M, Kelly DP, Holloszy JO. Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB J 16: 1879–1886, 2002.Crossref | PubMed | ISI | Google Scholar3 Calvo JA, Daniels TG, Wang X, Paul A, Lin J, Spiegelman BM, Stevenson SC, Rangwala SM. Muscle-specific expression of PPARγ coactivator-1α improves exercise performance and increases peak oxygen uptake. J Appl Physiol (January 31, 2008). doi:10.1152/japplphysiol.01231.2007.Link | ISI | Google Scholar4 Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur NK, Yan Z, Spiegelman BM. Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle specific knock-out animals. J Biol Chem 282: 30014–30021, 2007.Crossref | PubMed | ISI | Google Scholar5 Jorgensen SB, Richter EA, Wojtaszewski JFP. Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise. J Physiol 574: 17–31, 2006.Crossref | PubMed | ISI | Google Scholar6 Jäger S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proc Natl Acad Sci USA 104: 12017–12022, 2007.Crossref | PubMed | ISI | Google Scholar7 Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106:847–56, 2000.Crossref | PubMed | ISI | Google Scholar8 Leick L, Wojtaszewski JFP, Johansen ST, Kiilerich K, Comes G, Hellsten Y, Hidalgo J, Pilegaard H. PGC-1α is not mandatory for exercise- and training-induced adaptive gene responses in mouse skeletal muscle. Am J Physiol Endocrinol Metab 294: E463–E474, 2008.Link | ISI | Google Scholar9 Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418: 797–801, 2002.Crossref | PubMed | ISI | Google Scholar10 Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 1: 361–370, 2005.Crossref | PubMed | ISI | Google Scholar11 Pilegaard H, Saltin B, Neufer PD. Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol 546: 851–858, 2003.Crossref | PubMed | ISI | Google Scholar12 Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92: 829–839, 1998.Crossref | PubMed | ISI | Google Scholar13 Saltin B, Calbet JA. Point: in health and in a normoxic environment, V̇o2max is limited primarily by cardiac output and locomotor muscle blood flow. J Appl Physiol 100: 744–745, 2006.Link | ISI | Google Scholar14 Wende AR, Schaeffer PJ, Parker GJ, Zechner C, Han DH, Chen MM, Hancock CR, Lehman JJ, Huss JM, McClain DA, Holloszy JO, Kelly DP. A role for the transcriptional coactivator PGC-1alpha in muscle refueling. J Biol Chem 282: 36642–36651, 2007.Crossref | PubMed | ISI | Google Scholar15 Wu H, Kanatous SB, Thurmond FA, Gallardo T, Isotani E, Bassel-Duby R, Williams RS. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 296: 349–352, 2002.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: E. A. Richter, Copenhagen Muscle Research Centre, Dept. of Exercise and Sport Sciences, Univ. of Copenhagen, Copenhagen, Denmark (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited ByThe polymorphisms of the PPARD gene modify post-training body mass and biochemical parameter changes in women29 August 2018 | PLOS ONE, Vol. 13, No. 8Adaptation of Skeletal Muscles to Contractile Activity of Varying Duration and Intensity: The Role of PGC-1α11 June 2018 | Biochemistry (Moscow), Vol. 83, No. 6Expression of striated activator of rho-signaling in human skeletal muscle following acute exercise and long-term training4 March 2018 | Physiological Reports, Vol. 6, No. 5Genetik der Leistungsfähigkeit und Trainierbarkeit17 August 2017Acute simulated soccer-specific training increases PGC-1α mRNA expression in human skeletal muscle23 December 2014 | Journal of Sports Sciences, Vol. 33, No. 14PPAR-α and PPARGC1A gene variants have strong effects on aerobic performance of Turkish elite endurance athletes5 July 2014 | Molecular Biology Reports, Vol. 41, No. 9Genomic haplotype within the Peroxisome Proliferator-Activated Receptor Delta ( PPARD ) gene is associated with elite athletic status14 October 2013 | Scandinavian Journal of Medicine & Science in Sports, Vol. 24, No. 3An acute bout of high-intensity interval training increases the nuclear abundance of PGC-1α and activates mitochondrial biogenesis in human skeletal muscleJonathan P. 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Rennie1 June 2009 | Journal of Applied Physiology, Vol. 106, No. 6 More from this issue > Volume 104Issue 5May 2008Pages 1264-1265 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.90346.2008PubMed18323458History Published online 1 May 2008 Published in print 1 May 2008 Metrics
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