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