Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

PGC-1α and exercise in the control of body weight

International Journal of Obesity volume 36, pages 1428–1435 (2012)Cite this article

Subjects

Abstract

The increasing prevalence of obesity and its comorbidities represents a major threat to human health globally. Pharmacological treatments exist to achieve weight loss, but the subsequent weight maintenance is prone to fail in the long run. Accordingly, efficient new strategies to persistently control body weight need to be elaborated. Exercise and dietary interventions constitute classical approaches to reduce and maintain body weight, yet people suffering from metabolic diseases are often unwilling or unable to move adequately. The administration of drugs that partially mimic exercise adaptation might circumvent this problem by easing and supporting physical activity. The thermogenic peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) largely mediates the adaptive response of skeletal muscle to endurance exercise and is a potential target for such interventions. Here, we review the role of PGC-1α in mediating exercise adaptation, coordinating metabolic circuits and enhancing thermogenic capacity in skeletal muscle. We suggest a combination of elevated muscle PGC-1α and exercise as a modified approach for the efficient long-term control of body weight and the treatment of the metabolic syndrome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Bogers RP, Barte JC, Schipper CM, Vijgen SM, de Hollander EL, Tariq L et al. Relationship between costs of lifestyle interventions and weight loss in overweight adults. Obes Rev 2010; 11: 51–61.

    CAS  PubMed  Google Scholar 

  2. Wang Y, Beydoun MA, Liang L, Caballero B, Kumanyika SK . Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic. Obesity 2008; 16: 2323–2330.

    PubMed  Google Scholar 

  3. Kopelman PG . Obesity as a medical problem. Nature 2000; 404: 635–643.

    Article  CAS  PubMed  Google Scholar 

  4. Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E . 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. Cmaj 2007; 176: S1–S13.

    PubMed  PubMed Central  Google Scholar 

  5. Rosen ED, Spiegelman BM . Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006; 444: 847–853.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Muoio DM, Newgard CB . Obesity-related derangements in metabolic regulation. Ann Rev Biochem 2006; 75: 367–401.

    CAS  PubMed  Google Scholar 

  7. Dyson PA . The therapeutics of lifestyle management on obesity. Diabetes Obes Metab 2010; 12: 941–946.

    CAS  PubMed  Google Scholar 

  8. Horton ES . Effects of lifestyle changes to reduce risks of diabetes and associated cardiovascular risks: results from large scale efficacy trials. Obesity 2009; 17 Suppl 3: S43–S48.

    PubMed  Google Scholar 

  9. Stunkard AJ . Current views on obesity. Am J Med 1996; 100: 230–236.

    CAS  PubMed  Google Scholar 

  10. Bacon L, Aphramor L . Weight science: evaluating the evidence for a paradigm shift. Nutr J 2011; 10: 9.

    PubMed  PubMed Central  Google Scholar 

  11. Ayyad C, Andersen T . Long-term efficacy of dietary treatment of obesity: a systematic review of studies published between 1931 and 1999. Obes Rev 2000; 1: 113–119.

    CAS  PubMed  Google Scholar 

  12. Rosenbaum M, Leibel RL . Adaptive thermogenesis in humans. Int J Obes 2010; 34 Suppl 1: S47–S55.

    Google Scholar 

  13. Dulloo AG, Jacquet J, Seydoux J, Montani JP . The thrifty ‘catch-up fat’ phenotype: its impact on insulin sensitivity during growth trajectories to obesity and metabolic syndrome. Int J Obes 2006; 30 Suppl 4: S23–S35.

    CAS  Google Scholar 

  14. Weyer C, Walford RL, Harper IT, Milner M, MacCallum T, Tataranni PA et al. Energy metabolism after 2 y of energy restriction: the biosphere 2 experiment. Am J Clin Nutr 2000; 72: 946–953.

    CAS  PubMed  Google Scholar 

  15. Cettour-Rose P, Samec S, Russell AP, Summermatter S, Mainieri D, Carrillo-Theander C et al. Redistribution of glucose from skeletal muscle to adipose tissue during catch-up fat: a link between catch-up growth and later metabolic syndrome. Diabetes 2005; 54: 751–756.

    CAS  PubMed  Google Scholar 

  16. Summermatter S, Marcelino H, Arsenijevic D, Buchala A, Aprikian O, Assimacopoulos-Jeannet F et al. Adipose tissue plasticity during catch-up fat driven by thrifty metabolism: relevance for muscle-adipose glucose redistribution during catch-up growth. Diabetes 2009; 58: 2228–2237.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Dulloo AG . Regulation of fat storage via suppressed thermogenesis: a thrifty phenotype that predisposes individuals with catch-up growth to insulin resistance and obesity. Horm Res 2006; 65 (Suppl 3): 90–97.

    CAS  PubMed  Google Scholar 

  18. Chakravarthy MV, Booth FW . Eating, exercise, and “thrifty” genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J Appl Physiol 2004; 96: 3–10.

    PubMed  Google Scholar 

  19. Booth FW, Laye MJ, Lees SJ, Rector RS, Thyfault JP . Reduced physical activity and risk of chronic disease: the biology behind the consequences. Eur J Appl Physiol 2008; 102: 381–390.

    PubMed  Google Scholar 

  20. Matsakas A, Narkar VA . Endurance exercise mimetics in skeletal muscle. Curr Sports Med Rep 2010; 9: 227–232.

    PubMed  Google Scholar 

  21. Richter EA, Kiens B, Wojtaszewski JF . Can exercise mimetics substitute for exercise? Cell metabolism 2008; 8: 96–98.

    CAS  PubMed  Google Scholar 

  22. Finck BN, Kelly DP . PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 2006; 116: 615–622.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Jorgensen SB, Richter EA, Wojtaszewski JF . Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise. J Physiol 2006; 574 (Pt 1): 17–31.

    PubMed  PubMed Central  Google Scholar 

  24. Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M . Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. J Appl Physiol 2009; 106: 929–934.

    CAS  PubMed  Google Scholar 

  25. Handschin C . Regulation of skeletal muscle cell plasticity by the peroxisome proliferator-activated receptor gamma coactivator 1alpha. J Recept Signal Transduct Res 2010; 30: 376–384.

    CAS  PubMed  Google Scholar 

  26. Suwa M, Nakano H, Radak Z, Kumagai S . Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1alpha protein expressions in rat skeletal muscle. Metabolism 2008; 57: 986–998.

    CAS  PubMed  Google Scholar 

  27. Gurd BJ . Deacetylation of PGC-1alpha by SIRT1: importance for skeletal muscle function and exercise-induced mitochondrial biogenesis. Appl Physiol Nutr Metab 2011; 36: 589–597.

    CAS  PubMed  Google Scholar 

  28. Philp A, Chen A, Lan D, Meyer GA, Murphy AN, Knapp AE et al. Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-{gamma} coactivator-1{alpha} (pgc-1{alpha}) deacetylation following endurance exercise. J Biol Chem 2011; 286: 30561–30570.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Handschin C, Rhee J, Lin J, Tarr PT, Spiegelman BM . An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. Proc Natl Acad Sci U S A 2003; 100: 7111–7116.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Egan B, Carson BP, Garcia-Roves PM, Chibalin AV, Sarsfield FM, Barron N et al. Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. J Physiol 2010; 588 (Pt 10): 1779–1790.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Miura S, Kawanaka K, Kai Y, Tamura M, Goto M, Shiuchi T et al. An increase in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to exercise is mediated by beta-adrenergic receptor activation. Endocrinology 2007; 148: 3441–3448.

    CAS  PubMed  Google Scholar 

  32. Tadaishi M, Miura S, Kai Y, Kawasaki E, Koshinaka K, Kawanaka K et al. Effect of exercise intensity and AICAR on isoform-specific expressions of murine skeletal muscle PGC-1alpha mRNA: a role of beta-adrenergic receptor activation. Am J Physiol Endocrinol Metab 2011; 300: E341–E349.

    CAS  PubMed  Google Scholar 

  33. Norrbom JM, Sallstedt EK, Fischer H, Sundberg CJ, Rundqvist H, Gustafsson T . Alternative splice variant PGC-1{alpha}-b is strongly induced by exercise in human skeletal muscle. Am J Physiol Endocrinol Metab 2011; 301: E1092–E1098.

    CAS  PubMed  Google Scholar 

  34. Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O et al. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 2002; 418: 797–801.

    CAS  PubMed  Google Scholar 

  35. Summermatter S, Turnheer R, Santos G, Mosca B, Baum O, Treves S et al. Remodeling of calcium handling in skeletal muscle through PGC-1{alpha}: impact on force, fatigability and fiber type. Am J Physiol Cell Physiol 2012; 302: C88–C99.

    CAS  PubMed  Google Scholar 

  36. Handschin C, Choi CS, Chin S, Kim S, Kawamori D, Kurpad AJ et al. Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. J Clin Invest 2007; 117: 3463–3474.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur NK et al. Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. J Biol Chem 2007; 282: 30014–30021.

    CAS  PubMed  Google Scholar 

  38. Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G et al. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 2008; 451: 1008–1012.

    CAS  PubMed  Google Scholar 

  39. Pedersen BK . Muscles and their myokines. J Exp Biol 2011; 214 (Pt 2): 337–346.

    CAS  PubMed  Google Scholar 

  40. Summermatter S, Troxler H, Santos G, Handschin C . Coordinated balancing of muscle oxidative metabolism through PGC-1alpha increases metabolic flexibility and preserves insulin sensitivity. Biochem Biophys Res Commun 2011; 408: 180–185.

    CAS  PubMed  Google Scholar 

  41. Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 2008; 7: 45–56.

    CAS  PubMed  Google Scholar 

  42. Mihalik SJ, Goodpaster BH, Kelley DE, Chace DH, Vockley J, Toledo FG et al. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity 2010; 18: 1695–1700.

    CAS  PubMed  Google Scholar 

  43. An J, Muoio DM, Shiota M, Fujimoto Y, Cline GW, Shulman GI et al. Hepatic expression of malonyl-CoA decarboxylase reverses muscle, liver and whole-animal insulin resistance. Nat Med 2004; 10: 268–274.

    CAS  PubMed  Google Scholar 

  44. Houstis N, Rosen ED, Lander ES . Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 2006; 440: 944–948.

    CAS  PubMed  Google Scholar 

  45. Koves TR, Li P, An J, Akimoto T, Slentz D, Ilkayeva O et al. Peroxisome proliferator-activated receptor-gamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J Biol Chem 2005; 280: 33588–33598.

    CAS  PubMed  Google Scholar 

  46. Summermatter S, Baum O, Santos G, Hoppeler H, Handschin C . Peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) promotes skeletal muscle lipid refueling in vivo by activating de novo lipogenesis and the pentose phosphate pathway. J Biol Chem 2010; 285: 32793–32800.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Wende AR, Schaeffer PJ, Parker GJ, Zechner C, Han DH, Chen MM et al. A role for the transcriptional coactivator PGC-1alpha in muscle refueling. J Biol Chem 2007; 282: 36642–36651.

    CAS  PubMed  Google Scholar 

  48. Wende AR, Huss JM, Schaeffer PJ, Giguere V, Kelly DP . PGC-1alpha coactivates PDK4 gene expression via the orphan nuclear receptor ERRalpha: a mechanism for transcriptional control of muscle glucose metabolism. Mol Cell Biol 2005; 25: 10684–10694.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Choi CS, Befroy DE, Codella R, Kim S, Reznick RM, Hwang YJ et al. Paradoxical effects of increased expression of PGC-1alpha on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism. Proc Natl Acad Sci USA 2008; 105: 19926–19931.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Levine JA . Non-exercise activity thermogenesis (NEAT). Nutr Rev 2004; 62 (7 Pt 2): S82–S97.

    PubMed  Google Scholar 

  51. Levine JA, Lanningham-Foster LM, McCrady SK, Krizan AC, Olson LR, Kane PH et al. Interindividual variation in posture allocation: possible role in human obesity. Science 2005; 307: 584–586.

    Article  CAS  PubMed  Google Scholar 

  52. Dulloo AG, Seydoux J, Jacquet J . Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance. Physiol Behav 2004; 83: 587–602.

    CAS  PubMed  Google Scholar 

  53. Zurlo F, Larson K, Bogardus C, Ravussin E . Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest 1990; 86: 1423–1427.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. St-Pierre J, Lin J, Krauss S, Tarr PT, Yang R, Newgard CB et al. Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J Biol Chem 2003; 278: 26597–26603.

    CAS  PubMed  Google Scholar 

  55. O’Hagan KA, Cocchiglia S, Zhdanov AV, Tambuwala MM, Cummins EP, Monfared M et al. PGC-1alpha is coupled to HIF-1alpha-dependent gene expression by increasing mitochondrial oxygen consumption in skeletal muscle cells. Proc Natl Acad Sci U S A 2009; 106: 2188–2193.

    PubMed  PubMed Central  Google Scholar 

  56. Austin S, Klimcakova E, St-Pierre J . Impact of PGC-1alpha on the topology and rate of superoxide production by the mitochondrial electron transport chain. Free Radic Biol Med 2011; 51: 2243–2248.

    CAS  PubMed  Google Scholar 

  57. Calvo JA, Daniels TG, Wang X, Paul A, Lin J, Spiegelman BM et al. Muscle-specific expression of PPARgamma coactivator-1alpha improves exercise performance and increases peak oxygen uptake. J Appl Physiol 2008; 104: 1304–1312.

    CAS  PubMed  Google Scholar 

  58. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM . A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998; 92: 829–839.

    CAS  PubMed  Google Scholar 

  59. Cannon B, Nedergaard J . Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84: 277–359.

    CAS  PubMed  Google Scholar 

  60. Nedergaard J, Cannon B . The ‘novel’ ‘uncoupling’ proteins UCP2 and UCP3: what do they really do? Pros and cons for suggested functions. Exp Physiol 2003; 88: 65–84.

    CAS  PubMed  Google Scholar 

  61. MacLellan JD, Gerrits MF, Gowing A, Smith PJ, Wheeler MB, Harper ME . Physiological increases in uncoupling protein 3 augment fatty acid oxidation and decrease reactive oxygen species production without uncoupling respiration in muscle cells. Diabetes 2005; 54: 2343–2350.

    CAS  PubMed  Google Scholar 

  62. Cadenas S, Buckingham JA, Samec S, Seydoux J, Din N, Dulloo AG et al. UCP2 and UCP3 rise in starved rat skeletal muscle but mitochondrial proton conductance is unchanged. FEBS Lett 1999; 462: 257–260.

    CAS  PubMed  Google Scholar 

  63. Nabben M, Shabalina IG, Moonen-Kornips E, van Beurden D, Cannon B, Schrauwen P et al. Uncoupled respiration, ROS production, acute lipotoxicity and oxidative damage in isolated skeletal muscle mitochondria from UCP3-ablated mice. Biochimica et biophysica acta 2011; 1807: 1095–1105.

    CAS  PubMed  Google Scholar 

  64. Solinas G, Summermatter S, Mainieri D, Gubler M, Pirola L, Wymann MP et al. The direct effect of leptin on skeletal muscle thermogenesis is mediated by substrate cycling between de novo lipogenesis and lipid oxidation. FEBS Lett 2004; 577: 539–544.

    CAS  PubMed  Google Scholar 

  65. Solinas G, Summermatter S, Mainieri D, Gubler M, Montani JP, Seydoux J et al. Corticotropin-releasing hormone directly stimulates thermogenesis in skeletal muscle possibly through substrate cycling between de novo lipogenesis and lipid oxidation. Endocrinology 2006; 147: 31–38.

    CAS  PubMed  Google Scholar 

  66. Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 2003; 100: 8466–8471.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003; 34: 267–273.

    CAS  PubMed  Google Scholar 

  68. Choi S, Liu X, Li P, Akimoto T, Lee SY, Zhang M et al. Transcriptional profiling in mouse skeletal muscle following a single bout of voluntary running: evidence of increased cell proliferation. J Appl Physiol 2005; 99: 2406–2415.

    CAS  PubMed  Google Scholar 

  69. Handschin C, Kobayashi YM, Chin S, Seale P, Campbell KP, Spiegelman BM . PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Gene Dev 2007; 21: 770–783.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Geng T, Li P, Yin X, Yan Z . PGC-1alpha promotes nitric oxide antioxidant defenses and inhibits FOXO signaling against cardiac cachexia in mice. Am J Pathol 2011; 178: 1738–1748.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Liang H, Balas B, Tantiwong P, Dube J, Goodpaster BH, O’Doherty RM et al. Whole body overexpression of PGC-1alpha has opposite effects on hepatic and muscle insulin sensitivity. Am J Physiol Endocrinol Metab 2009; 296: E945–E954.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Steinberg GR, Watt MJ, McGee SL, Chan S, Hargreaves M, Febbraio MA et al. Reduced glycogen availability is associated with increased AMPKalpha2 activity, nuclear AMPKalpha2 protein abundance, and GLUT4 mRNA expression in contracting human skeletal muscle. Appl Physiol Nutr Metab 2006; 31: 302–312.

    CAS  PubMed  Google Scholar 

  73. Wojtaszewski JF, Jorgensen SB, Hellsten Y, Hardie DG, Richter EA . Glycogen-dependent effects of 5-aminoimidazole-4-carboxamide (AICA)-riboside on AMP-activated protein kinase and glycogen synthase activities in rat skeletal muscle. Diabetes 2002; 51: 284–292.

    CAS  PubMed  Google Scholar 

  74. Richter EA, Ruderman NB . AMPK and the biochemistry of exercise: implications for human health and disease. Biochem J 2009; 418: 261–275.

    CAS  PubMed  Google Scholar 

  75. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S et al. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 2006; 127: 397–408.

    CAS  PubMed  Google Scholar 

  76. O’Neill HM, Maarbjerg SJ, Crane JD, Jeppesen J, Jorgensen SB, Schertzer JD et al. AMP-activated protein kinase (AMPK) {beta}1{beta}2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proc Natl Acad Sci USA 2011; 108: 16092–16097.

    PubMed  PubMed Central  Google Scholar 

  77. Chambers MA, Moylan JS, Smith JD, Goodyear LJ, Reid MB . Stretch-stimulated glucose uptake in skeletal muscle is mediated by reactive oxygen species and p38 MAP-kinase. J Physiol 2009; 587 (Pt 13): 3363–3373.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Lefort N, St-Amand E, Morasse S, Cote CH, Marette A . The alpha-subunit of AMPK is essential for submaximal contraction-mediated glucose transport in skeletal muscle in vitro. Am J Physiol Endocrinol Metab 2008; 295: E1447–E1454.

    CAS  PubMed  Google Scholar 

  79. Merry TL, Lynch GS, McConell GK . Downstream mechanisms of nitric oxide-mediated skeletal muscle glucose uptake during contraction. Am J Physiol Regul Integr Comp Physiol 2010; 299: R1656–R1665.

    CAS  PubMed  Google Scholar 

  80. Zhang SJ, Sandstrom M, Ahlsen M, Ivarsson N, Zhu H, Ma J et al. 2-Methoxyoestradiol inhibits glucose transport in rodent skeletal muscle. Exp Physiol 2010; 95: 892–898.

    CAS  PubMed  Google Scholar 

  81. Fernandez C, Hansson O, Nevsten P, Holm C, Klint C . Hormone-sensitive lipase is necessary for normal mobilization of lipids during submaximal exercise. Am J Physiol Endocrinol Metab 2008; 295: E179–E186.

    CAS  PubMed  Google Scholar 

  82. Prats C, Donsmark M, Qvortrup K, Londos C, Sztalryd C, Holm C et al. Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine. J Lipid Res 2006; 47: 2392–2399.

    CAS  PubMed  Google Scholar 

  83. Ivy JL . Muscle glycogen synthesis before and after exercise. Sports Med 1991; 11: 6–19.

    CAS  PubMed  Google Scholar 

  84. Janiszewski PM, Ross R . Physical activity in the treatment of obesity: beyond body weight reduction. Appl Physiol Nutr Metab 2007; 32: 512–522.

    PubMed  Google Scholar 

  85. Musi N, Hirshman MF, Arad M, Xing Y, Fujii N, Pomerleau J et al. Functional role of AMP-activated protein kinase in the heart during exercise. FEBS Lett 2005; 579: 2045–2050.

    CAS  PubMed  Google Scholar 

  86. 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 2000; 106: 847–856.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Qi Z, He J, Su Y, He Q, Liu J, Yu L et al. Physical exercise regulates p53 activity targeting SCO2 and increases mitochondrial COX biogenesis in cardiac muscle with age. PLoS One 2011; 6: e21140.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Boveris A, Navarro A . Systemic and mitochondrial adaptive responses to moderate exercise in rodents. Free Radic Biol Med 2008; 44: 224–229.

    CAS  PubMed  Google Scholar 

  89. Little JP, Safdar A, Benton CR, Wright DC . Skeletal muscle and beyond: the role of exercise as a mediator of systemic mitochondrial biogenesis. Appl Physiol Nutr Metab 2011; 36: 598–607.

    CAS  PubMed  Google Scholar 

  90. Lira VA, Benton CR, Yan Z, Bonen A . PGC-1alpha regulation by exercise training and its influences on muscle function and insulin sensitivity. Am J Physiol Endocrinol Metab 2010; 299: E145–E161.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Miura S, Kai Y, Ono M, Ezaki O . Overexpression of peroxisome proliferator-activated receptor gamma coactivator-1alpha down-regulates GLUT4 mRNA in skeletal muscles. J Biol Chem 2003; 278: 31385–31390.

    CAS  PubMed  Google Scholar 

  92. Miura S, Tomitsuka E, Kamei Y, Yamazaki T, Kai Y, Tamura M et al. Overexpression of peroxisome proliferator-activated receptor gamma co-activator-1alpha leads to muscle atrophy with depletion of ATP. Am J Pathol 2006; 169: 1129–1139.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Handschin C . The biology of PGC-1alpha and its therapeutic potential. Trends Pharmacol Sci 2009; 30: 322–329.

    CAS  PubMed  Google Scholar 

  94. McCarty MF . Up-regulation of PPARgamma coactivator-1alpha as a strategy for preventing and reversing insulin resistance and obesity. Med Hypotheses 2005; 64: 399–407.

    CAS  PubMed  Google Scholar 

  95. Puigserver P, Spiegelman BM . Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 2003; 24: 78–90.

    CAS  PubMed  Google Scholar 

  96. Russell LK, Mansfield CM, Lehman JJ, Kovacs A, Courtois M, Saffitz JE et al. Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner. Circ Res 2004; 94: 525–533.

    CAS  PubMed  Google Scholar 

  97. Bergouignan A, Rudwill F, Simon C, Blanc S . Physical inactivity as the culprit of metabolic inflexibility: evidences from bed-rest studies. J Appl Physiol 2011; 111: 1201–1210.

    CAS  PubMed  Google Scholar 

  98. Garland Jr T, Schutz H, Chappell MA, Keeney BK, Meek TH, Copes LE et al. The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives. J Exp Biol 2011; 214 (Pt 2): 206–229.

    PubMed  Google Scholar 

  99. Hamilton MT, Hamilton DG, Zderic TW . Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes 2007; 56: 2655–2667.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Our research is supported by grants from the Swiss National Science Foundation (SNF PP00A-110746), the Muscular Dystrophy Association USA (MDA), the SwissLife ‘Jubiläumsstiftung für Volksgesundheit und medizinische Forschung’, the Swiss Society for Research on Muscle Diseases (SSEM), the Swiss Diabetes Association, the Roche Research Foundation, the United Mitochondrial Disease Foundation (UMDF), the Association Française contre les Myopathies (AFM), and the University of Basel. The funders had no role in the preparation of the manuscript.

Author information

Authors and Affiliations

  1. Division of Pharmacology/Neurobiology, Biozentrum, University of Basel, Basel, Switzerland

    S Summermatter & C Handschin

Authors
  1. S Summermatter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Handschin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Handschin.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Summermatter, S., Handschin, C. PGC-1α and exercise in the control of body weight. Int J Obes 36, 1428–1435 (2012). https://doi.org/10.1038/ijo.2012.12

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2012.12

Keywords

This article is cited by

Search

Advanced search

Quick links