Extended Data Fig. 1: Decreased Nrg4 resulted in increased endothelial dysfunctions and impaired metabolic profiles.
(A-D)The correlation between plasma Nrg4 and vascular endothelium-dependent (A) and -independent (B) dilation function in human (n = 60) and mice (n = 10) (C, D). (E) The levels of BAT Nrg4 mRNA in mice (n = 10, *P < 0.001). (F) The levels of inflammatory cytokines and adhesion molecules mRNA levels in MAECs of aortas (n = 10 biologically independent animals, *P < 0.001). (G) The level of Nrg4 in blood and Nrg4 protein expression in BAT, kidney, WAT, liver, muscle and endothelium cells (EC) (H) in KO and WT mice (n = 3, *P < 0.001). (I)The mRNA expression of Nrg4 in the same tissues in (H) (n = 3, *P < 0.001). (J) The experiment schedule for the effects of Nrg4 deficiency on endothelial function, endothelial inflammation and metabolic profiles in WT and KO mice (6 mice in each group). (K) Body weight (n = 6, *P < 0.01 vs. KO-NCD; #P < 0.01 vs. KO-WD). (L) Results of GTT (n = 6) and the AUC for GTT using the trapezoidal rule (*P < 0.01 vs. KO-NCD; #P < 0.01 vs. KO-WD). (M) Results of normalized ITT as a percentage of fasting glucose (n = 6) and the AUC for ITT (*P < 0.01 vs. KO-NCD; #P < 0.01 vs. KO-WD). KO and WT mice aged 6 weeks were divided into four groups (WT-NCD, KO-NCD, WT-WD and KO-WD) and were fed their respective diets for 12 weeks (6 mice in each group). For a, b, c, d, Pearson correlations were used to identify correlations between variables. For e, f, g, i, p values were calculated by two-sided t-test. For k, l, m, p values were calculated by two-sided t-test or one-way ANOVA with Tukey’s multiple-comparison test. Data were shown as mean ± SEM.
