Tau deficiency inhibits an anorexigenic effect of brain insulin administration leading to metabolic disturbances. (A) Cumulative food intake for 24 h measured using metabolic cages in tau KO and littermate controls intracerebroventricularly injected first with vehicle and then 2 µl insulin (5 mg/ml; ***, P < 0.001 vs. WT-PBS; °°°, P < 0.001 vs. tau KO/insulin; two-way ANOVA). (B) Cumulated food intake in WT and tau KO mice 24 h after vehicle or insulin brain injection (same animals as in A; *, P < 0.05; **, P < 0.01 vs. WT-PBS; #, P < 0.05 vs. WT/insulin; °°°, P < 0.001 vs. tau KO/insulin; one-way ANOVA, LSD Fisher’s post-hoc test). (C) 48-h body weight variation after vehicle or insulin brain injection in tau KO and WT littermates (same animals as in A; °°°, P < 0.001 vs. tau KO/insulin; two-way ANOVA). Data in A–C show mean ± SEM from 5–10 mice per group from three independent experiments. (D) Mean food intake (*, P < 0.05, two-way ANOVA). (E) Ambulatory activity (*, P < 0.05, two-way ANOVA). (F) Body weight gain (***, P < 0.05, two-way ANOVA). (G) Plasma leptin levels (**, P < 0.01, Student’s t test). (H and I) Adipose tissue weight (*, P < 0.05; **, P < 0.01, Student’s t test). (J) Glycemia. (K) Insulinemia (*, P < 0.05, Student’s t test). (L) Intraperitoneal glucose tolerance test (***, P < 0.05, two-way ANOVA) in tau KO mice and littermate controls. Quantifications represent mean ± SEM. Controls are indicated as open circles/bars, tau KO as black circles/bars. Dashed lines/bars represent insulin-treated animals. Mice were 6–8 mo old at time of experiments and sacrifice. Metabolic data in C–L show mean ± SEM from 10–12 (D), 9–12 (E), 13–27 (F), 4–5 (G), 11–14 (H and I), 15–17 (J), 20–23 (K), and 12–14 (L) mice per group acquired from three independent experiments.