Extended Data Fig. 2. HDAC6-specific Weight Loss response to HDAC6 inhibitors.
a, Growth curves of WT (n=18 mice) and HDAC6 KO (n=12 mice) mice on high fat diet (left) and their body composition (right). b, Body weight of daily vehicle (n=5) or tubastatin (i.p., 12.5 mg/kg, n-6) treated DIO HDAC6 KO mice. c, Structure of tubastatin and BRD3067 (top). Immunoblots from 293T lysates 24hr after drug treatment. d, e, Body weight (BRD3067 vs. TubA P=7.0E-3, Veh vs. TubA P=2.0E-3) and food intake (day 1 BRD3067 vs. TubA P=5.8E-4, Veh vs. TubA P=9.7E-9, day 2 BRD3067 vs. TubA P=2.6E-5, Veh vs. TubA P=2.8E-7, day 3 BRD3067 vs. TubA P=9.5E-3, Veh vs. TubA P=2.6E-5, day 4 BRD3067 vs. TubA P=1.7E-5, Veh vs. TubA P=3.0E-8, day 5 BRD3067 vs. TubA P=4.7E-5, Veh vs. TubA P=6.2E-9, day 6 BRD3067 vs. TubA P=2.0E-3, Veh vs. TubA P=3.4E-9, Veh vs. BRD3067 P=1.8E-3, day 7 BRD3067 vs. TubA P=8.5E-4, Veh vs. TubA P=1.4E-6, two-way ANOVA with Tukey post-hoc test) of vehicle, tubastatin, or BRD3067-treated DIO wild-type mice (n=6). f, g, Body weight change of DIO wild-type mice treated daily with vehicle (n=12), ricolinostat (25 mg/kg, i.p., n=12, P=2.7E-7 by two-way ANOVA with Sidak correction) (f) or CAY10603 (12.5 mg/kg, i.p., n=4, P=2.5E-9 by two-way ANOVA with Sidak correction) (g). h, i, Weight change (P=9.2E-4) and cumulative food intake (P=8.9E-6 by two-way ANOVA with Sidak correction for h and i) of wild-type and HDAC6 KO DIO mice treated daily with i.p. CAY10603 (n=3). *P<0.05, **P<0.01, ***P<0.001 as analyzed by two-way analysis of variance (ANOVA) with Sidak’s correction Tukey’s post-hoc test for multiple comparison. Data are represented as mean ± s.e.m.