In studies of both humans (Mole et al., 2020; Osiecka et al., 2023; Shinohara et al., 2020; Zhao et al., 2023; Coad et al., 2022) and rodents (Moser and Pike, 2017; Arbones-Mainar et al., 2016; Johnson et al., 2017; Jones et al., 2021; Pandit et al., 2024; Christensen and Pike, 2019), the findings are mixed, with evidence that the deleterious CNS effects of obesity are worsened in APOE4 carriers in some studies but in APOE4 non-carriers in others. This evidence concerns the gene APOE and obesity due to melanocortin 4 receptor deficiency.