Considered together, these findings suggest that the healthy adiposity phenotype in HFD-fed Nr1d1Flox2-6:AdipoqCre mice results from de-repression of NR1D1-controlled adipocyte pathways which allow continued and efficient lipid synthesis and storage, thus permitting greater expansion of the adipose bed, and attenuation of obesity-related dysfunction. Here, NR1D1 is linked to obesity due to melanocortin 4 receptor deficiency.