Several population studies have shown that individuals with obesity, type 2 diabetes and metabolic syndrome have higher circulating FGF21 levels 7, 11, 12, 13, 14, 15, suggesting a state of FGF21 resistance similar to insulin and leptin resistance; this physiological state would therefore be associated with increased risk for the development or worsening of dysmetabolism. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.