Fig. 5: Hepatic ESRRA facilitates lactate consumption and reduces histone lactylation in an LDHB-dependent manner.
a–c Protein levels of LDHB, LDHA, H3K18la and H3K9la (a), relative LDH activity (b) and lactate levels (c) in the livers from Ldhbfl/fl mice treated with either Ad-Cre or Ad-GFP. n = 6 mice. d Glucose production assay supported by Lac as the substrate in Ldhbfl/fl hepatocytes infected with Ad-Cre or Ad-GFP, pretreated for 2 h with 20 μM H89 and then costimulated with or without 50 μM Bt2-cAMP. n = 4. e Schematic diagram displaying the experimental procedure of LTT, treadmill exercise and Ad-Cre/GFP administration for Ldhbfl/fl male mice. f,g Blood lactate at indicated time points and the corresponding AUC for LTT (f) and treadmill exercise (g). n = 6 mice. h–j Running curves (h), total time (i) and distance (j) to exhaustion on treadmill. n = 6 mice. k Schematic diagram showing the experimental procedure for Ldhbfl/fl mice infected with Ad-GFP, or Ad-ESRRA with or without Ad-Cre. n = 7 mice. l,m Blood lactate excursion curves and the corresponding AUC for LTT (l) and treadmill exercise (m) from mice in k. n = 7 mice. n–p Running curves (n), time (o) and distance (p) to exhaustion on treadmill. n = 7 mice. q Western blot analysis of hepatic protein levels. r Relative lactate-to-pyruvate LDH activity of mice livers in k. n = 7 mice. Statistical analysis was performed using a two-tailed Student’s t-test (b, c, f, g, i and j), two-way ANOVA with Tukey’s post hoc test (d, l, m, o, p and r) and log-rank test (h and n). *P < 0.05, **P < 0.01 and ***P < 0.001. Schematic created in BioRender: e, Created in BioRender. Tongling, H. (2026) https://BioRender.com/jubpp8j; k, Created in BioRender. Tongling, H. (2026) https://BioRender.com/1i0zsoj.
