Altered DNA methylation in promoters of transcription factor genes (PPARA, KLF15, NR3C1, RORA and ATF4) known to regulate FGF21 expression and its binding receptors and co-factors (FGFR1, FGFR3 and FGFRL1 and KLB) has been revealed in relation to the elevated levels of circulating FGF21 in obesity. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.