Peroxisome proliferator-activated receptor-gamma coactivator-1alpha in muscle links metabolism to inflammation.
1. In higher eukaryotes, metabolism and immunity are tightly coupled. However, whereas in evolutionary terms a compromised immune response due to undernourishment has been the predominant problem, the inflammatory response to obesity and other lifestyle-associated diseases has increased in relevance in Western societies in the past 100 years. 2. Traditionally, fat tissue has been considered as the major source of pro-inflammatory secreted factors in these pathologies. However, in recent years the contribution of other tissues to disease-causing chronic inflammation has been increasingly appreciated. 3. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) is one of the key regulatory factors in active skeletal muscle. Aberrant expression of PGC-1alpha in inactive muscle fibres could be linked to a sedentary lifestyle, persistent systemic inflammation and a higher risk for many chronic diseases. Accordingly, modulation of PGC-1alpha activity in skeletal muscle may have a broad range of therapeutic effects. Here, recent advances in the understanding of the role of muscle PGC-1alpha in health and disease are reviewed.
Handschin
Christoph
C
Biozentrum, University of Basel, Basel and Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. christoph.handschin@unibas.ch
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D008660:Metabolism / Q000502:physiology*; D008954:Models, Biological; D009043:Motor Activity / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology; D009220:Myositis / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors