Importantly, C3 and ASP were upregulated in the plasma of 6-week-old Par-4-/- and AKO mice before the onset of adipocyte hypertrophy relative to Par-4+/+ mice (Figures 5C–E), implying that C3/ASP were elevated before the onset of obesity at 3 months. This evidence concerns the gene F2RL3 and obesity due to melanocortin 4 receptor deficiency.