Exercise and PGC-1α in inflammation and chronic disease

A sedentary lifestyle is a strong and independent risk factor for many chronic diseases. In most cases, inadequate levels of physical activity are linked to a persistent, sterile inflammation, both locally in various organs as well as systemically. Inversely, exercise is an efficient intervention for the prevention and treatment of various pathologies. Despite this obvious importance, the molecular mechanisms that underlie exercise‐induced health benefits remain largely unclear. In recent years, the peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) has emerged as a regulatory nexus of muscle adaptation to endurance exercise. Muscle PGC‐1α not only promotes an oxidative, slow‐twitch muscle fiber type, but also modulates the phenotype of non‐muscle cells. For example, activation of epithelial cells contributes to PGC‐1α‐controlled muscle vascularization. Similarly, a muscle PGC‐1α‐dependent signaling results in a remodeling of the active zone of motor neurons at the neuromuscular junction. Intriguingly, PGC‐1α also reduces pro‐inflammatory gene expression in muscle and most likely other cell types. Thus, a bidirectional negative regulation of PGC‐1α and the nuclear factor κB (NF‐κB) might provide the molecular basis for the mutual antagonism between oxidative metabolism and inflammation in muscle. In this review, we summarize the regulation and function of these transcriptional regulators with a particular focus on exercise and inflammation in skeletal muscle.