OBJECTIVE:Recent studies have demonstrated that 1,3-diacylglycerol (1,3-DAG) has several metabolic advantages over triacylglycerol (TAG) in humans and in animal models despite both oils having a similar fatty acid composition. In our current study, we have examined the effects of long-term feeding of a 1,3-DAG-rich oil on the dyslipidemia and atherosclerosis in the experimental model of the diabetic apolipoprotein E (apoE)-deficient mouse that develops accelerated atherosclerosis. METHODS AND RESULTS:Diets containing 1,3-DAG-rich oil or TAG oil were administered to control non-diabetic apoE-dificient and diabetic apoE-deficient mice for 20 weeks. In diabetic apoE-deficient mice, 1,3-DAG reduced the extent of atherosclerotic lesions in the aortic arch and thoracic aorta by 37 and 44%, respectively, compared to TAG. Further, in diabetic apoE-deficient mice, plasma total cholesterol and triglyceride levels were significantly lower in the 1,3-DAG-fed group than in the TAG-fed group. This occurred partially through an apparent reduction in the size of triglyceride-rich lipoproteins but not apparently by reducing the number of lipoprotein particles. By contrast the control non-diabetic apoE-deficient mice showed no differential responses to the type of oil at least over 20 weeks. CONCLUSIONS:We have demonstrated that dietary 1,3-DAG-rich oil reduced atherosclerosis in diabetic apoE-deficient mice, and was associated with reduction in plasma cholesterol especially within larger triglyceride-rich lipoproteins.