Obesity is a central feature of the metabolic syndrome and is associated with increased risk for insulin resistance and type II diabetes. Here, we investigated the contribution of human apoliprotein E3 and mouse apoli-protein E to the development of diet-induced obesity in response to western-type diet. Our data show that apolipoprotein E contributes to the development of obesity and other related metabolic disorders, and that human apolipoprotein E3 is more potent than mouse apolipoprotein E in promoting obesity in response to western-type diet. .