When fed an energy-dense high-fat diet (HFD; with a macronutrient composition that is comparable to that of human diets), Ldlr-/-.Leiden mice develop obesity, insulin resistance and dyslipidemia in addition to atherosclerosis, with the involvement of adipose tissue inflammation and increased gut permeability (Gart et al., 2021, 2022a; van den Hoek et al., 2021). This evidence concerns the gene LDLR and obesity due to melanocortin 4 receptor deficiency.