Briefly, exercise causes an increase circulating irisin protein levels and/or FNDC5 mRNA expression in some (Bostrom et al., 2012; Huh et al., 2012; Brenmoehl et al., 2014), but not all studies (Huh et al., 2012; Kurdiova et al., 2014; Timmons et al., 2012; Timmons et al., 2005; Gallagher et al., 2010; Seo et al., 2014), whereas, obesity has either a positive (Polyzos et al., 2013; Huh et al., 2012; Timmons et al., 2012) or a negative (Seo et al., 2014; Peterson et al., 2008b) association with irisin/FNDC5. The gene discussed is FNDC5; the disease is Obesity.