Fig. 1

Ketogenic diet leads to weight gain and glucose intolerance in male and female mice. A Body weight was measured prior to diet intervention and weekly thereafter until the end of the experiment, at 26 weeks. Difference in body weight was assessed using a mixed effects model for high glycemic index (HGD) and ketogenic (KD) diets relative to control diet (CD). B Fasting glucose was measured following a 4-h morning fast at 26 weeks. C Mice were injected with a glucose solution and blood glucose was measured at 15-, 30-, 60-, and 120-min post injection. Area under the curve (AUC) for the glucose tolerance test (GTT) was calculated as an index of whole glucose excursion. D Male mice on the KD first displayed impaired glucose tolerance at 10 weeks, which did not correspond to weight gain, while E female mice on the KD first showed impaired glucose at 14 weeks, coinciding with significant weight gain. All data are shown as mean ± SEM and n = 5–11 per group. Statistical differences for weight over time were calculated with a mixed effects model. One-way ANOVA followed a Dunnett’s test was used to compare multiple groups (A–C) and a Student’s t test was used to compare two groups (D, E). For all statistical tests, *, **, ***, ****p < 0.05, 0.01, 0.001, and 0.0001, respectively