However, diet-induced obesity was proposed as an FGF21-resistant state, including attenuated FGF21 signaling response as assessed by extracellular mitogen-activated protein kinase 1 and 2 (ERK1/2) phosphorylation as well as an impaired induction of FGF21 target genes, including cFos and EGR1 in both liver and fat20. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.