Fig. 1

FGF21 deficiency alters systemic metabolites linked to mitochondrial and cardiac energetic defects. a–c Heatmap of significantly altered serum metabolites, including mitochondrial FAO precursors, fatty acids and oxylipins, TCA cycle intermediates, and nucleosides, in Fgf21^−/− (n = 3) and WT (n = 3) mice. p < 0.05; fold change (FC) > 1.5 or < 0.67. See also Fig. S1a–c and S1e. For changes in serum phosphocreatine levels, see Fig. S1d. S, supplementary. d Experimental procedure for electrocardiogram analysis under anesthesia and anabiosis simulating ‘sleep’ (anesthesia on) and ‘awakening’ (anesthesia off) stages of torpor. ‘Sleep’, a sedentary state under anesthetic inhalation; Awakening, a recovery and active state following anesthetic removal. e Heart rate (HR) changes in Fgf21^−/− (n = 95) vs WT (n = 56) mice measured in d under normal conditions. BPM, beats per minute. f Area-under-curve (AUC) analysis of the HR excursion curves in e. See Fig. S2a. g, h Echocardiogram analysis of the mechano-energetic efficiency (MEE), ejection fraction (EF) and cardiac output (CO) of Fgf21^-/- (n = 51) vs WT (n = 51) mice. See Fig. S2b-S2h for other Echo parameters. i Telemetry monitoring of HR changes over 24 hours in representative Fgf21^-/- vs WT mice under normal conditions. j AUC analysis of cumulative HR excursion curves of Fgf21^-/- (n = 6) vs WT (n = 6) mice in i. Changes in ambulatory movement and body temperature are shown in Fig. S2j-S2l. k Representative TEM images of left ventricle cross-sections from Fgf21^-/- vs WT mice under normal conditions. Yellow arrowhead, mitochondria. Cyan arrowhead, Z line. See Fig. S3e for broader, low-magnification images. The changes in cardiac morphometric parameters, mild dilatation and insignificant fibrosis are shown in Fig. S3. l Mitochondrial DNA content of hearts from Fgf21^-/- (n = 11-12) vs WT (n = 12) mice. m Catalytic activities of mitochondrial complexes I-IV in the hearts of Fgf21^-/- (n = 7-9) vs WT (n = 7-9) mice. h, hour. n, o HR Changes (n) with rhFGF21 treatment (n = 12) and AUC analysis (o) of Fgf21^-/- (n = 78) vs WT (n = 47) mice under normal conditions. p, q Changes in EF and LVSED with rhFGF21 treatment (n = 22) in Fgf21^-/- (n = 51) vs WT (n = 51) mice, as in n. See Fig. S3g-S3i for other parameters. The data are presented as the means ± s.e.m.s. (a–c, e–j) Two-tailed unpaired Student’s t-test; (l–q) ordinary one-way ANOVA followed by Tukey’s test; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. *, Fgf21^-/- vs WT groups by Student’s t test or one-way ANOVA. ^$, between treatment groups in WT mice. ^#, between treatment groups in Fgf21^-/- mice. All these also apply to other figures