1. In higher eukaryotes, metabolism and immunity are tightly coupled. However, whereas evolutionary, a compromised immune response due to
undernourishment has been the predominant problem, the inflammatory response to obesity and other life style-associated diseases gained in relevance in Western societies in the last hundred years.
2. Traditionally, fat tissue has been considered as the major source of proinflammatory 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 fibers 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.