Detailed comparison of our animals shows that although both transgenic models overexpress the transcriptional active N-terminal domain of SREBP-1a in the liver to a comparable degree, overexpressing of the functional SREBP-1a wild type shows a vast accumulation of lipids in the liver including obesity and insulin resistance, whereas the phosphorylation deficient alb–SREBP–1aΔP mice is protected. Here, SREBF1 is linked to obesity due to melanocortin 4 receptor deficiency.