Fig. 7
From: A two-strata energy flux system driven by a stress hormone prioritizes cardiac energetics
FGF21 orchestrates cardiac energy flux by engaging the LKB1-AMPK-mTOR energy stress pathways. a Transcriptomic enrichment of the LKB1-AMPK and mTOR energy regulation pathways in the hearts of fasted Fgf21-/- (n = 3) vs WT (n = 3) mice and those with rhFGF21 treatment (n = 3). b Representative Western blot analysis of total kinase activities of cardiac LKB1, AMPK, and mTOR in the indicated mice (n = 3-6 for each group). Total kinase activity = (p-Kinase/Kinase) x (Kinase/Beta-actin), see also Fig. S29a. c Effects of cardiac-specific Stk11 (LKB1) ablation (Stk11f/f;Myh6Cre) on HR. AUC analysis on the right. See Fig. S29b for experimental scheme, Fig. S29c for the AUC in the ‘Sleep’ and Awakening phases, and Fig. S29d for the Echo parameters. d Representative Western blot analysis of total kinase activities of cardiac AMPK, and mTOR in the indicated groups of mice (n = 3-6 for each group). See Fig. S29e. e Expression of representative genes involved in the TCA cycle, ETC, OXPHOS, and heart contraction in fasted Stk11f/f;Myh6Cre and Fgf21-/- mice 2 hours after rhFGF21 treatment. For changes in cardiac myofibrillar and mitochondrial structure, see Fig. S30a. f Effects of mTOR inhibitor Torin-1 (0.05 mg per mouse, i.p.) on rhFGF21-induced HR improvements in fasted Fgf21-/- mice (n = 11-12 per group). See Fig. S29f, g for experimental scheme and total AUC. g Effects of Torin-1 and liver-specific Hmgcs2 deficiency on the cardiac ATP content in acute rhFGF21-treated Fgf21-/- mice (n = 6 per group) following 12-h and 24-h fasts, respectively. h Effects of the AMPK activator AICAR (1.25 mg/mouse, i.p.) (n = 6) on rhFGF21-induced HR improvements in fasted Fgf21-/- mice (n = 12 and 17, respectively). See Fig. S30b-S30c for experimental scheme and total AUC, and Fig. S30d for the Echo parameters. i Transcriptomic enrichment of mitophagy, macroautophagy and associated LKB1-AMPK-mTOR energy stress pathways in the mice as in a. See Fig. S30e, f for mitophagy regulation by LKB1-AMPK-mTOR and autophagosome assembly. Data are means ± s.e.m.s; (d, e) Two-tailed unpaired Student’s t-test; (a–c, f-i) ordinary one-way ANOVA followed by Tukey’s test
