In the present study, we show that HF feeding (60% kcal from fat and 0.15% cholesterol) induces obesity, hypercholesterolemia, inflammatory disorders and endothelial dysfunction in young (10-wk-old at the beginning of the treatment) ApoE−/− mice fed a HF diet for only 8 weeks. Here, APOE is linked to obesity due to melanocortin 4 receptor deficiency.