LEP and obesity due to melanocortin 4 receptor deficiency: Interestingly, the relationship between leptin and TGFβ could be bidirectional, since TGFβ/SMAD3 signaling appears to be crucial for the development of obesity, as demonstrated in mice in which TGFβ signaling was blocked or that were deficient in SMAD3 and consequently were protected from developing obesity34,35.