TGF-β levels are reported to increase with adiposity in overweight (BMI between 25-29.9 kg/m2) and obese (BMI ≥ 30 kg/m2) subjects compared to the normal subjects with BMI less than 24.9 kg/m2), and systemic blockade of TGF-β/SMAD3 signaling resulted in protection against diet-induced obesity in experimental mice (13). This evidence concerns the gene SMAD3 and obesity due to melanocortin 4 receptor deficiency.