Pioglitazone is known to improve hyperglycemia, reduce hyperinsulinemia, and ameliorate hypertriglyceridemia in a variety of animal models of obesity and insulin resistance [22, 21, 20, 19, 18]; however, pioglitazone did not reverse the alterations in lysosomal enzymes and in fact lead to a further increase in the levels of cathepsin D in the cytosol. This evidence concerns the gene CTSD and obesity due to melanocortin 4 receptor deficiency.