In contrast to NPs, some myokines produced by skeletal muscles and myocardium, mainly irisin, apelin and adropin, are associated with metabolic abnormalities including hyperglycemia, insulin resistance and skeletal muscle metabolism, adipose tissue browning in T2DM with adverse cardiac remodeling, skeletal muscle weakness/myopathy and finally HFpEF [9]. The gene discussed is FNDC5; the disease is type 2 diabetes mellitus.