Extended Data Fig. 6: Decreased SM BCAA oxidation is specific and does not affect body weight or glucose tolerance on HFD.

a, Plasma labeling of BCAAs after U¹³C-BCAAs gavage (fraction) in 5-hr fasted mice; n = 8 Dbt^l/l (WT) and n = 8 Dbt^l/l-HSA-CreER (Cre). b, BCKDH complex activity measured in fasted quads from n = 4 WT and n = 4 Cre mice. Labeling fraction of TCA cycle intermediates 10 min after gavage of U¹³C-BCAAs in c, liver d, iBAT, & e, gWAT in 5-hr fasted mice; n = 8 WT and n = 8 Cre. f, Body weights; n = 10 WT and n = 14 Cre. g, Lean mass; n = 7 WT and n = 13 Cre. Fasting plasma pool size of various amino acids during steady-state infusion of U¹³C-BCAAs before (basal, 5-hr fasted) and during (clamp, 7-hr fasted) HIEC in n = 6 WT and n = 6 Cre mice. h, Plasma BCAA concentration in 5-hr fasted or 2-hr re-fed after an overnight fast in mice; n = 8 WT and n = 10 Cre. i, Steady-state plasma labeling of BCAAs by infusion of U¹³C-BCAAs before (basal) and during (clamp) HIEC; n = 6 WT and n = 6 Cre mice fed. j, 1.5 g/kg glucose IP-GTT in 5-hr fasted mice fed HFD for 4 weeks; n = 8 WT and n = 9 Cre. k, Area-under-the-curve (AUC) for the GTT in j. l, Insulin concentration at t = 0 and t = 20 min (n = 8 WT and n = 9 Cre) during the GTT from j. m, Plasma BCAA concentration in 5-hr fasted mice before (t = 0), n = 8 WT and n = 9 Cre, and 20 min after (t = 20), n = 6 WT and n = 7 Cre, a gavage of BCAAs. Mice used in these experiments were male, aged 10–20 weeks fed HFD for 4–8 weeks. Data are presented as means ± SEM. Comparisons of two groups use two-tailed Student’s t-test. Experiments with multiple comparisons at different time-points use two-way ANOVA with repeated measures.