FGF21 and obesity due to melanocortin 4 receptor deficiency: The term “FGF21 resistance” was first used to describe increased circulating FGF21 levels concomitant to decreased FGF21 receptor complex expression in white adipose tissue of obese mice.  Since this initial report, the term has been associated with a wide range of pathological states, including human obesity, in which circulating FGF21 levels are elevated.