A collaborative investigation in parallel to this study with our mouse model deficient in adipose FGFR1 reveals that, under conditions of diet-induced obesity (DIO) and FGF21 administration, adipose tissue expressing FGFR1-KLB accounts for nearly the entirety of beneficial metabolic effects of FGF21 in vivoa. Here, FGFR1 is linked to obesity due to melanocortin 4 receptor deficiency.