In obesity (OB) and type 2 diabetes mellitus (T2DM), dysregulated myokine profiles characterized by reduced levels of irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B (CTSB) have been reported and may contribute to the development of both sarcopenia and cognitive impairment. Here, BDNF is linked to obesity due to melanocortin 4 receptor deficiency.