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PGC-1α-mediated adaptations in skeletal muscle

  • Muscle Physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative effects of transient gene responses to each single exercise, but how is this regulated? A potential candidate in this is the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, which has been identified as a master regulator of mitochondrial biogenesis, but also been shown to regulate proteins involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1α transcription and potentially PGC-1α activity through post-translational modifications, and concomitant PGC-1α-mediated gene regulation is suggested to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1α-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise training, and describes functional significance of PGC-1α-mediated effects in skeletal muscle. In addition, regulation of PGC-1α expression and activity in skeletal muscle is described. The impact of changes in PGC-1α expression in mouse skeletal muscle and the ability of PGC-1α to regulate multiple pathways and functions underline the potential importance of PGC-1α in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1α-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle and concomitant impaired metabolism.

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Acknowledgements

The PGC-1α-related work in the authors' laboratory is supported by the Lundbeck Foundation, the Novo Nordisk Foundation and the Danish Medical Research Council. The Centre of Inflammation and Metabolism is supported by The Danish National Research Foundation (grant 02-512-555). CIM is part of the UNIK Project: Food, Fitness and Pharma for Health and Disease, supported by the Danish Ministry of Science, Technology and Innovation. The Copenhagen Muscle Research Centre is supported by a grant from the Capital Region of Denmark.

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  1. Department of Biology, Centre of Inflammation and Metabolism, Copenhagen Muscle Research Centre, University of Copenhagen, August Krogh Building, Universitetsparken 13, 2100, Copenhagen Ø, Denmark

    Jesper Olesen, Kristian Kiilerich & Henriette Pilegaard

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  1. Jesper Olesen
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Correspondence to Henriette Pilegaard.

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Olesen, J., Kiilerich, K. & Pilegaard, H. PGC-1α-mediated adaptations in skeletal muscle. Pflugers Arch - Eur J Physiol 460, 153–162 (2010). https://doi.org/10.1007/s00424-010-0834-0

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