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 life style-associated diseases has increased in relevance in Western societies in the last hundred years. 2. Traditionally, fat tissue has been considered as the major source of pro-inflammatory secreted factors in these pathologies. In recent years however, the contribution of other tissues to a disease-causing chronic inflammation has been increasingly appreciated. 3. The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is one of the key regulatory factors in the active skeletal muscle. Aberrant expression of PGC-1α in inactive muscle fibres could link a sedentary life style, persistent systemic inflammation and the higher risk for many chronic diseases. Modulation of PGC-1α activity in skeletal muscle might accordingly have a broad therapeutic effect. Here, recent advances in the understanding of the role of muscle PGC-1α in health and disease are reviewed
