However, muscle anabolic resistance is exacerbated with obesity and thus the combination of obesity with older age leads to a near non-existent elevation of the MPS response to amino acid provision beyond basal levels, which may be associated with a plethora of factors including; reduced physical activity and a low relative proportion of lean mass, intracellular lipotoxicity and elevated inflammation, impaired muscle regeneration, insulin resistance, impaired endocrine function, impaired anabolic signaling etc. (85, 187, 188). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.