To gain mechanistic insights on the molecular basis for changed metabolism and how FGF21 controls obesity resistance, next-generation RNA sequencing of all genotypes was performed in metabolically active tissues (BAT, iWAT, liver, and muscle) after three weeks of HFD (Fig. 5), before the divergence of body weights (Fig. 2b). The gene discussed is FGF21; the disease is obesity due to melanocortin 4 receptor deficiency.