Similar to 2 weeks after diet, the index of pIRS1S636/Y1222 and pIRS1S307/Y1222, representative of impaired insulin signaling, increased nearly three-fold and five-fold, respectively, in the HF mice compared with the CTRL mice after 24 weeks of diet; however, dietary intervention improved this effect in the HF16 mice (Fig 4A and 4B). This evidence concerns the gene INS and hydrops fetalis.