FGF21 and obesity due to melanocortin 4 receptor deficiency: Because FGF21 enters the systemic circulation, it is able to integrate metabolism across liver, adipose tissue, skeletal muscle, pancreas, and other metabolic organs (Figure 2), by controlling expression of transcriptional programs that shape cellular phenotype and tissue metabolic function, ultimately exerting anti-obesity, anti-diabetic, and anti-hyperlipidemic effects in rodents and primates (43, 44).