In light of the diverse modifications, the concordant finding that FoxO1,3,4 genetic inactivation and insulin resistance — a state of proposed FoxO activation — resulted in similar reductions in Apom mRNA strongly suggest that FoxO-dependent transcription is paradoxically inactivated at the Apom locus in the insulin-resistant models tested (db/db, Western diet, and gold thioglucose–induced hypothalamic injury). This evidence concerns the gene FOXO1 and Insulin resistance.