Fig. 6
From: A two-strata energy flux system driven by a stress hormone prioritizes cardiac energetics
FGF21 promotes peripheral and transcardiac metabolic flux to meet cardiac energy needs during prolonged fasting. a, b Expression analysis of representative genes in hepatic ketogenesis pathway by qRT-PCR in Fgf21-/- (n = 5) vs WT mice (n = 5), under basal, 24-h fast, and acute rhFGF21 treatment (n = 5) conditions. For the response to rhFGF21, see Fig. S25a. For the 12-h fast effects, see Fig. S25b. The bar symbols follow those in Fig. 5b. For pathway changes in FFAs sourced from WAT lipolysis, see Fig. S27a-S27c. c Changes in serum beta-hydroxybutyrate (BHB) and FFAs in Fgf21-/- (n = 7-12) vs WT mice (n = 8-12) after fasting (both 12-h and 24-h) and rhFGF21 treatment (n = 7-12). For serum glucose and TG, see Fig. S26a. d Effects of hepatic Hmgcs2 knockdown (KD) on rhFGF21-promoted improvement of HR in Fgf21-/- mice subjected to a 24-h fast compared with control AAV (n = 6-9 per group). Right: AUC of HR excursion curves; see Fig. S26b, c for more details. For the Echo parameters, see Fig. S26d. e Changes of serum BHB levels upon hepatic Hmgcs2 KD and rhFGF21 treatment in Fgf21-/- mice after a 24-h fast. f Effects of adipocyte-specific ablation of Fgfr1 (Fgfr1f/f;AdipoqCreERT) on the improvement of HR promoted by acute rhFGF21 treatment or AAV9-TBG-hFGF21 mediated overexpression (hFGF21OE) in mice fasted for 24 hours (n = 11-12 per group). OE, overexpression. hFGF21, human FGF21 coding sequence. Right: AUC analysis, in which star symbols for p-values without underlines indicate a comparison to Fgfr1-ablated mice under normal conditions (baseline). See Fig. S28a for experimental scheme and S28b for the Echo parameters. g Changes of serum FFAs in Fgfr1f/f;AdipoqCreERT mice. h Effects of the ATGL inhibitor Atglistatin (1.42 mg/mouse, i.p.) on the rhFGF21-promoted improvement of HR in Fgf21-/- mice fasted for 12 hours (n = 11-12 per group). See Fig. S28c for experimental scheme and notes, Fig. S28d for more comparisons, and Fig. S28e for the Echo parameters. i Effects of Atglistatin on the rhFGF21-promoted increases in serum FFAs in Fgf21-/- mice fasted for 12 hours (n = 9-10 per group), from which the heart draws FFA fuel. Data are means ± s.e.m.s; (d, g, h) Two-tailed unpaired Student’s t-test; (b, c, e, f, i) ordinary one-way ANOVA followed by Tukey’s test. (a) Image is generated in PowerPoint
