Both βKlotho (an essential co-factor for FGF21 signalling) mRNA (data not shown) and protein levels was significantly decreased in obese hearts [P<0.05 vs.lean; Figure 5C1], further supporting the concept of decreased FGF21/FGF-R1/βKlotho signalling in obesity. This evidence concerns the gene FGFR1 and obesity due to melanocortin 4 receptor deficiency.