Considering the elevated serum FGF21 levels in metabolic disorders such as T2DM and obesity, and the potential association with FGF21 resistance, artificially increasing the levels of FGF21 (or FGF21 analogs) may not necessarily enhance their actual biological effects in such states of metabolic disruption. The gene discussed is FGF21; the disease is obesity due to melanocortin 4 receptor deficiency.