Tg6-mice have enhanced endothelial nitric oxide synthase activity to regulate the resultant elevated blood viscosity21 that may provide an indirect EPO activity to improve metabolism as mice with overexpression of endothelial nitric oxide synthase exhibit resistance to diet-induced obesity and adipose tissue with increased metabolic activity and altered lipid metabolism64. This evidence concerns the gene EPO and obesity due to melanocortin 4 receptor deficiency.