Although expression of PGC-1α increases immediately in response to aerobic exercise (Wright et al., 2007; De Filippis et al., 2008; Harber et al., 2010; Donges et al., 2012), the same response is not evident in muscle of humans with obesity (De Filippis et al., 2008). The gene discussed is PPARGC1A; the disease is obesity due to melanocortin 4 receptor deficiency.