APOE and obesity due to melanocortin 4 receptor deficiency: Furthermore, although both ApoE−/− and human APOE2 gene replacement mice are more sensitive than wild type mice to diet-induced hyperlipidemia, the ApoE−/− mice are resistant to diet-induced obesity [113] whereas human APOE2 gene replacement mice are similar to human ε2 carriers and are more sensitive than wild type mice to develop obesity in response to a high fat diet [111].