Differentiating preadipocytes with low C/EBPα and PPARγ can still accumulate lipid when exposed to fatty acids but are insulin resistant and dysfunctional, consistent with accretion of the large, insulin-resistant, C/EBPα- and PPARγ-deficient fat cells in obesity that are associated with diabetes (Xie et al., 2006; Kim et al., 2007). Here, PPARG is linked to obesity due to melanocortin 4 receptor deficiency.