The stark difference in progression and severity of diet-induced obesity is likely due (at least in part) to the HFD-induced hyperphagia, which is observed in Nr1d1-/- mice (WT food intake 2.92±0.10 g HFD/day/mouse; KO 3.74±0.21 g, p=0.0014, Student’s t-test, n=21/genotype), but not in Nr1d1Flox2-6:AdipoqCre mice (Cre-ve 2.99±0.61 g HFD/day/mouse; Cre+ve 3.01±0.60 g, p>0.05, n=8/genotype). This evidence concerns the gene NR1D1 and obesity due to melanocortin 4 receptor deficiency.