Human data synthesized by Orioli and Thissen indicate that obesity and type 2 diabetes are characterized by an altered muscle secretome, with increased release of pro-inflammatory myokines (IL-6, IL-8, IL-15, TNF-α, MCP-1) and growth regulators such as myostatin and follistatin, changes that parallel chronic activation of inflammatory pathways and impaired oxidative/AMPK–PGC-1α signaling in skeletal muscle, as demonstrated by systematic human clinical evidence [68]. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.