FNDC5 and metabolic disease: Irisin is mainly secreted in skeletal (Boström et al., 2012) and cardiac muscle tissue (Aydin et al., 2014), and is implicated in modulation of mitochondrial function and energy balance (Ouyang et al., 2020; Xin et al., 2020) lipid and glucose metabolism (Perakakis et al., 2017; Wang et al., 2020), and amelioration of impaired cardiac function in some metabolic disorders (Wang et al., 2017; Jiang et al., 2021).