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. This evidence concerns the gene FOS and obesity due to melanocortin 4 receptor deficiency.