Here we report the application of this integrated approach to study the significance of sex on the genetic determinants of obesity and the associated regulation of liver gene expression in an F2 intercross derived from the inbred strains C57BL/6J (B6) and C3H/HeJ (C3H) on an apolipoprotein E null (ApoE−/−) background. This evidence concerns the gene APOE and obesity due to melanocortin 4 receptor deficiency.