Following 12 months of HF-HS diet, Ppara I-KO mice had reduced adiposity (Fig. 3h), and improved oral glucose tolerance (Supplementary Fig. 8d); hence, intestinal PPARα depletion ameliorated the diet-induced obesity independently of the type and length of the high-caloric diet. This evidence concerns the gene PPARA and obesity due to melanocortin 4 receptor deficiency.