In addition to providing insight into the mechanisms of leptin action on the hippocampus and on their disruption in HFD, our work can be linked to the facts that metabolic alterations are now recognized as risk factors for Alzheimer’s disease (AD) (McGuire and Ishii, 2016) and that transgenic mouse models of AD display altered levels of circulating leptin, along with a reduction of its effects on hypothalamic neurons (Ishii et al., 2014). Here, LEP is linked to early-onset autosomal dominant Alzheimer disease.