The effect of downregulating total RGS proteins in obesity has been studied, demonstrating a block in weight gain and insulin resistance in homozygous Gαi2G184S knock-in male mice, which express RGS-insensitive Gαi2 with a G184S mutation that blocks RGS protein binding and GTPase acceleration, fed an HF [8]. This evidence concerns the gene PITX2 and obesity due to melanocortin 4 receptor deficiency.