For example, in experimental murine studies of obesity-related insulin resistance, an increased loss of muscle mass occurs via insulin receptor substrate-1/phosphatidylinositol-3-kinase Akt pathway down-regulation47; since adiponectin inhibits the muscle degradation that occurs via this pathway48, the decreased adiponectin concentrations that arise in individuals with obesity might be contributory. Here, IRS1 is linked to obesity due to melanocortin 4 receptor deficiency.