IRS1 and obesity due to melanocortin 4 receptor deficiency: In 2020, Li et al highlighted that the adipocyte tissue–derived exosomal miRNA miR-222 promotes obesity-associated insulin resistance affecting the liver and skeletal muscle of high-fat diet–fed obese mice by suppressing the expression of insulin receptor substrate 1 (IRS-1), an intracellular signaling adapter protein that mediates many key metabolic signals initiated by insulin and its receptors and is the main substrate of insulin-like growth factor 1 (IGFR1) [39, 40].