Consistent with the healthier metabolic phenotype observed in obese Nr1d1Flox2-6:AdipoqCre mice, we found that the large majority of the 863 NR1D1 gene targets unmasked by HFD feeding are normally repressed in obesity (Figure 6E), with 551 (63.8%) showing a significant down-regulation in obese control (Cre-ve) animals (chronic HFD compared to NC-fed state). The gene discussed is NR1D1; the disease is obesity due to melanocortin 4 receptor deficiency.