In particular both the mice haploinsufficient for SMRT and mice with a targeted disruption of the first receptor interaction domain (RID) of SMRT have developed obesity, hepatic steatosis, and insulin resistance, but their phenotype only manifested in the context of a high fat diet (HFD)[7, 32, 33]. This evidence concerns the gene NCOR2 and obesity due to melanocortin 4 receptor deficiency.