This is striking inasmuch as under our experimental conditions both adipose and hepatic tissues undergo pathological alterations of energy metabolism leading to obesity and hepatic steatosis The interest of our animal model (long-term treatment with a relatively mild, 45% kcal from fat, HFD from the early adolescence) deals with the fact that HFD mice display diabetes, obesity, and hyperleptinemia together with a generalized state of leptin resistance that does not involve cardiac tissue (10). This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.