Notably, controlled exercise studies in people with obesity and T2DM have revealed no significant alterations in myocellular expression or systemic levels of key myokines (including IL-6, IL-15, FGF21, and angiopoietin-like 4) compared to lean controls, challenging the notion that dysregulation of these myokines underpins insulin resistance in human skeletal muscle [192,193]. This evidence concerns the gene IL6 and obesity due to melanocortin 4 receptor deficiency.