An intriguing possibility is that a chronic release of this molecule in the obesity status could lead to an S100A4 resistant situation, in a similar way to what has been shown for other molecules including leptin and FGF21.27, 28 Further studies are warranted to determine the occurrence of an S100A4 resistant state in obesity. The gene discussed is FGF21; the disease is obesity due to melanocortin 4 receptor deficiency.