Here, we demonstrate that Dgat1 deficiency solely in enterocytes is sufficient to protect ApoE−/− mice from diet-induced hypercholesterolemia and atherosclerosis, suggesting that the loss of Dgat1 in the small intestine is crucial for the resistance to atherosclerosis development in global Dgat1−/−ApoE−/− mice. The gene discussed is DGAT1; the disease is atherosclerosis.