Additionally, the persistence of insulin resistance in CR versus HF-LF mice could influence the relative differences in leptin signaling observed for specific brain regions for these treatment groups, as leptin and insulin signaling pathways are convergent via effects on PI3 kinase [41], and increased insulin signaling has been demonstrated to inhibit leptin STAT3 signaling in the hypothalamus [42]. This evidence concerns the gene STAT3 and Insulin resistance.