In mice, we previously demonstrated that chronic hyperinsulinemia down-regulates myocardial UCP3 content by 40% through induction of pathway-selective insulin resistance, increased recruitment of the sterol regulatory element-binding protein (SREBP)-1 transcription factor at the UCP3 promoter, and transcriptional repression of the UCP3 gene [31]. The gene discussed is SREBF1; the disease is Hyperinsulinemia.