Recently, DIO3OS was found to preprogram intergenerational brown fat development and obesity resistance in mice via cis regulation of DIO3.[38] We found that DIO3OS could modulate ZEB1 in a trans manner, and that ZEB1 is important in obesity,[39, 40] suggesting that DIO3OS may also contribute to obesity by regulating ZEB1 in trans. This evidence concerns the gene DIO3 and obesity due to melanocortin 4 receptor deficiency.