The relative level of PGC-1α in skeletal muscle is determined by physical activity. PGC-1α, in turn, controls muscle fiber adaptation to exercise and confers a number of beneficial changes. As a result, a reduction of systemic inflammation is observed in exercised individuals, possibly mediated through elevation of PGC-1α. In contrast, inactivity, and thus low skeletal muscle PGC-1α, results in a chronic inflammatory state and thereby causes serious pathological consequences. This inactivity-driven systemic inflammation is further exacerbated by obesity.