β-secretase (Beta-site APP Cleaving Enzyme 1 – BACE1) is a key player in the development and progression of Alzheimer’s disease. Amyloid Precursor Protein (APP) is sequentially cleaved by β- then γ-secretase resulting in the production of the β-amyloid (Aβ) peptide, which aggregates and forms the major component of senile plaques found in the brains of all Alzheimer’s Disease (AD) patients. BACE1 has been validated as a therapeutic target for AD as BACE1 knockout (KO) mice have reduced Aβ levels while being viable and fertile. Recent reports have demonstrated altered body weights in young BACE1 KO mice. Here we measured body weight of BACE1 KO mice over a period of several months. The results show that the BACE1 KO mice were leaner than their wildtype (wt) littermate controls over this period. The significant differences observed led us to challenge the phenotype with a high fat diet (58% fat). The BACE1 KO mice gained significantly less weight than wt controls. We measured Peri-genital fat (PGF) weight, food intake and insulin sensitivity to help determine the source of the decreased weight gain. Our results suggest an interesting link between BACE1 and body weight.