Fig. 1 |. Systemic BCAA oxidation improves insulin sensitivity.

a, Western blotting of tissues from n = 6 vehicle and n = 6 BT2-treated mice (14-3-3 is the loading control). b,c, Plasma BCAA concentrations (n = 10 vehicle and n = 10 BT2-treated) (b) and plasma BCKA levels (n = 10 vehicle and n = 10 BT2-treated) (c) in mice fasted for 5 h or refed for 2 h after overnight fasting. d, Intraperitoneal GTT (IP-GTT, 1.5 g kg⁻¹) in mice fasted for 5 h after acute BT2 treatment; n = 10 vehicle and n = 10 BT2-treated mice on HFD for 5 weeks. e, AUC for the GTT in d. f, Insulin concentration at t = 0 and t = 20 (n = 10 vehicle and n = 9 BT2-treated mice) during the acute BT2 treatment GTT from d. a–f, Acute BT2 treatment was achieved via gavage with 100 mg kg⁻¹ of either vehicle or BT2 the night before and the morning of the experiment. g, Glucose IP-GTT (1.5 g kg⁻¹) in mice fasted for 5 h after chronic BT2 treatment; n = 10 vehicle and n = 10 BT2-treated mice on HFD for 4 weeks. h, AUC for the GTT in g. i, Insulin concentration at t = 0 and t = 20 min (n = 10 vehicle and n = 9 BT2-treated mice) during chronic BT2 treatment GTT from g. g–i, Chronic BT2 treatment was achieved via 50 mg kg⁻¹ day⁻¹ gavage of mice treated with either vehicle or BT2 for 4 weeks. Mice used for these experiments were male C57BL/6J diet-induced obesity (DIO) mice aged 10–12 weeks and fed HFD for 4–6 weeks. Data are presented as the mean ± s.e.m. When two groups were compared, a two-tailed Student’s t-test was used, with significance defined as *P < 0.05, **P < 0.01 and ***P < 0.001. In the experiments with multiple comparisons at different time points, a repeated measures, two-way analysis of variance (ANOVA) was used with significance defined as *P < 0.05. b, Valine fasted P = 0.000012; valine refed P = 0.000092; leucine fasted P < 0.000001; leucine refed P = 0.000129; isoleucine fasted P < 0.000001; isoleucine refed P = 0.000031. c, KIC/KMV fasted P = 0.000023; KIC/KMV refed P = 0.001194; KIV fasted P = 0.000011; KIV refed P = 0.000062. d, 60 min P = 0.0227; 120 min P = 0.0142. e, P = 0.003179. h, P = 0.009880. i, 0 min P = 0.027731; 20 min P = 0.045392.