Hostname: page-component-8448b6f56d-42gr6 Total loading time: 0 Render date: 2024-04-24T22:24:18.326Z Has data issue: false hasContentIssue false
  • English
  • Français

Involvement of PPARγ co-activator-1, nuclear respiratory factors 1 and 2, and PPARα in the adaptive response to endurance exercise

Published online by Cambridge University Press:  05 March 2007

Keith Baar
Keith Baar*
Affiliation:
Department of Mechanical Engineering and Institute of Gerontology, University of Michigan, Ann Arbor, MI, 48109–2007, USA
*
Corresponding author: Dr Keith Baar, Fax: +1 734 936 2116, Email: kbaar@umich.edu
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.

Endurance exercise training induces an increase in the respiratory capacity of muscle, resulting in an increased capacity to generate ATP as well as improved efficiency of muscle contraction. Such adaptations are largely the result of a coordinated genetic response that increases mitochondrial proteins, fatty acid oxidation enzymes and the exercise- and insulin-stimulated glucose transporter GLUT4, and shifts the contractile and regulatory proteins to their more efficient isoforms. In recent years a number of the transcriptional regulators involved in this genetic response have been identified and these factors can be classified into two different groups. The first group comprises transcription factors such as nuclear respiratory factors (NRF) 1 and 2 and PPARα that bind DNA in a sequence-specific manner. The second group, referred to as transcriptional co-activators, alter transcription without directly binding to DNA. The PPARγ co-activator (PGC) family of proteins have been identified as the central family of transcriptional co-activators for induction of mitochondrial biogenesis. PGC-1α is activated by exercise, and is sufficient to produce the endurance phenotype through direct interactions with NRF-1 and PPARα, and potentially NRF-2. Furthering the understanding of the activation of PGC proteins following exercise has implications beyond improving athletic performance, including the possibility of providing targets for the treatment of frailty in the elderly, obesity and diseases such as mitochondrial myopathies and diabetes.

Keywords

Mitochondrial biogenesisSkeletal muscleTranscriptional co-activators
Type
Symposium 3: Mechanisms involved in exercise-induced mitochondrila biogenesis in skeletal muscle
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 2 , May 2004 , pp. 269 - 273
Copyright
Copyright © The Nutrition Society 2004

References

Andersson, U & Scarpulla, RC (2001) Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Molecular and Cellular Biology 21, 3738–3749.CrossRefGoogle ScholarPubMed
Baar, K, Song, Z, Semenkovich, CF, Jones, TE, Han, DH, Nolte, LA, Ojuka, EO, Chen, M & Holloszy, JO (2003) Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity. FASEB Journal 17, 1666–1673.Google Scholar
Baar, K, Wende, AR, Jones, TE, Marison, M, Nolte, LA, Chen, M, Kelly, DP & Holloszy, JO (2002) Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1. FASEB Journal 16, 1879–1886.CrossRefGoogle ScholarPubMed
Boss, O, Bachman, E Vidal-Puig, A, Zhang, CY, Peroni, O & Lowell, BB (1999) Role of the beta(3)-adrenergic receptor and/or a putative beta(4)-adrenergic receptor on the expression of uncoupling proteins and peroxisome proliferator-activated receptor-gamma coactivator-1. Biochemical and Biophysical Research Communications 261, 870–876.CrossRefGoogle Scholar
Burzynski, SR (2003) Gene silencing – a new theory of aging. Medical Hypotheses 60, 578–583.CrossRefGoogle ScholarPubMed
Czubryt, MP McAnally, J, Fishman, GI & Olson, EN (2003) Regulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) and mitochondrial function by MEF2 and HDAC5. Proceedings for the National Academy of Sciences USA 100, 1711–1716.Google Scholar
Gulick, T, Cresci, S, Caira, T, Moore, DD & Kelly, DP (1994) The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proceedings for the National Academy of Sciences USA 91, 11012–11016.Google Scholar
Holloszy, JO (1967) Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle. Journal of Biological Chemistry 242, 2278–2282.CrossRefGoogle ScholarPubMed
Holloszy, JO, Kohrt, WM & Hansen, PA (1998) The regulation of carbohydrate and fat metabolism during and after exercise. Frontiers in Bioscience 3, D1011–D1027.Google Scholar
Hood, DA (2001) Contractile activity-induced mitochondrial biogenesis in skeletal muscle. Journal of Applied Physiology 90, 1137–1157.CrossRefGoogle ScholarPubMed
Horowitz, JF, Leone, TC, Feng, W, Kelly, DP & Klein, S (2000) Effect of endurance training on lipid metabolism in women: a potential role for PPARalpha in the metabolic response to training. American Journal of Physiology 279, E348–E355.Google Scholar
Irrcher, I, Adhihetty, PJ, Sheehan, T, Joseph, AM & Hood, DA (2003) PPARgamma coactivator-1alpha expression during thyroid hormone- and contractile activity-induced mitochondrial adaptations. American Journal of Physiology 284, C1669–C1677.Google Scholar
Lin, J, Puigserver, P, Donovan, J, Tarr, P & Spiegelman, BM (2002 a) Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta), a novel PGC-1-related transcription coactivator associated with host cell factor. Journal of Biological Chemistry 277, 1645–1648.CrossRefGoogle ScholarPubMed
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 (2002 b) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418, 797–801.Google Scholar
Michael, LF, Wu, Z, Cheatham, RB, Puigserver, P, Adelmant, G, Lehman, JJ, Kelly, DP & Spiegelman, BM (2001) Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proceedings for the National Academy of Sciences USA 98, 3820–3825.Google Scholar
Miura, S, Kai, Y, Ono, M & Ezaki, O (2003) Overexpression of peroxisome proliferator-activated receptor g coactivator-1 a (PGC-1a) down-regulates GLUT4 mRNA in skeletal muscles. Journal of Biological Chemistry 278, 31385–31390.CrossRefGoogle Scholar
Nisoli, E, Clementi, E, Paolucci, C, Cozzi, V, Tonello, C, Sciorati, C, Bracale, R, Valerio, A, Francolini, M, Moncada, S & Carruba, MO (2003) Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299, 896–899.Google Scholar
Pilegaard, H, Saltin, B & Neufer, PD (2003) Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. Journal of Physiology (London) 546, 851–858.CrossRefGoogle ScholarPubMed
Puigserver, P, Rhee, J, Lin, J, Wu, Z, Yoon, JC, Zhang, CY, Krauss, S, Mootha, VK, Lowell, BB & Spiegelman, BM (2001) Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Molecular Cell 8, 971–982.Google Scholar
Puigserver, P & Spiegelman, BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha): Transcriptional coactivator and metabolic regulator. Endocrinology Reviews 24, 78–90.Google Scholar
Puigserver, P, Wu, Z, Park, CW, Graves, R, Wright, M & Spiegelman, BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92, 829–839.Google Scholar
Reichmann, H, Hoppeler, H Mathieu-Costello, O, von Bergen, F & Pette, D (1985) Biochemical and ultrastructural changes of skeletal muscle mitochondria after chronic electrical stimulation in rabbits. Pflugers Archiv 404, 1–9.CrossRefGoogle ScholarPubMed
Ren, JM, Semenkovich, CF, Gulve, EA, Gao, J & Holloszy, JO (1994) Exercise induces rapid increases in GLUT4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscle. Journal of Biological Chemistry 269, 14396–14401.Google Scholar
Rooyackers, OE, Adey, DB, Ades, PA & Nair, KS (1996) Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle. Proceedings for the National Academy of Sciences USA 93, 15364–15369.Google Scholar
Scarpulla, RC (2002) Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochimica et Biophysica Acta 1576, 1–14.Google Scholar
Terada, S, Goto, M, Kato, M, Kawanaka, K, Shimokawa, T & Tabata, I (2002) Effects of low-intensity prolonged exercise on PGC-1 mRNA expression in rat epitrochlearis muscle. Biochemical and Biophysical Research Communications 296, 350–354.CrossRefGoogle ScholarPubMed
Vega, RB, Huss, JM & Kelly, DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Molecular and Cellular Biology 20, 1868–1876.Google Scholar
Vogel, JL & Kristie, TM (2000) The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP. EMBO Journal 19, 683–690.Google Scholar
Wibom, R, Hultman, E, Johansson, M, Matherei, K Constantin-Teodosiu, D & Schantz, PG (1992) Adaptation of mitochondrial ATP production in human skeletal muscle to endurance training and detraining. Journal of Applied Physiology 73, 2004–2010.Google Scholar