High-fat diet-induced obese mice switched to a low-fat diet produce β-hydroxybutyrate preceding weight loss. Mice were fed a low-fat diet (LFD) or a high-fat diet (HFD) for 16 wk and then either maintained on the same diets or switched (day 0) from the HFD to a LFD (HFDtoLFD) for 3 additional weeks. Body weight (A), urine β-hydroxybutyrate (BHB) (B), and visceral adipose tissue (VAT) weight at day 23 (C) were measured. In a separate cohort of HFDtoLFD mice, blood β-hydroxybutyrate (BHB) was measured daily (D); n = 5 mice/group. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001, comparing HFDtoLFD and HFD (A and B), compared with HFD group (C), or compared with day 0 (D).