Fig. 5
TLR4 is required for the action of S100A9 on hyperketonemia and survival in ID. In DT-treated pLIVE-S100A9 RIP-DTR; Tlr4+/+-, DT-treated pLIVE-S100A9 RIP-DTR; Tlr4−/−-, DT-untreated (healthy) RIP-DTR; Tlr4+/+-, and DT-untreated (healthy) pLIVE-S100A9 RIP-DTR; Tlr4−/− mice: a plasma insulin level (n/group = 6, 6, 5, and 5); b glycemia (n/group = 6, 5, 15, and 6), and c plasma β-hydroxybutyrate content (n/group = 3, 5, 4, and 6). In DT-treated pLIVE-S100A9 RIP-DTR; Rage+/+-, DT-treated pLIVE-S100A9 RIP-DTR; Rage−/−-, DT-untreated (healthy) RIP-DTR; Rage+/+-, and DT-untreated (healthy) pLIVE-S100A9 RIP-DTR; Rage−/− mice: d plasma insulin level,(n/group = 5, 6, 6, and 6); e glycemia (n/group = 10, 9, 11, and 9) and f plasma β-hydroxybutyrate content (n/group = 11, 8, 10, and 6). Error bars represent SEM. Statistical analyses have been performed by two-way ANOVA (Tukey’s post hoc test) *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. Kaplan–Meier survival analyses (g–i). According to Log-Rank Mantel Cox test as well as Gehan-Beslow Wilcoxon test, DT-pLIVE-S100A9 mice (n = 16) have higher survival as compared to pLIVE controls (n = 12) (g). DT-pLIVE-S100A9 Tlr4−/− (n = 9) have similar lifespan as DT-pLIVE Tlr4+/+ controls (n = 11) while DT-pLIVE-S100A9 Tlr4+/+ (n = 11) have higher survival compared to the latter (h). DT-pLIVE-S100A9 Rage−/− (n = 9) and DT-pLIVE-S100A9 Rage+/+ (n = 11) have similar lifespan which is extended compared to DT-pLIVE Rage+/+ controls (n = 8) (i). In g ***P < 0.001 DT-pLIVE mice vs DT-pLIVE-S100A9 mice. In h ***P < 0.001; DT-pLIVE-S100A9 RIP-DTR; Tlr4+/+ mice vs. DT-pLIVE RIP-DTR; Tlr4+/+ mice; $$P < 0.01; DT-pLIVE-S100A9 RIP-DTR; Tlr−/− mice vs. DT-pLIVE-S100A9 RIP-DTR; Tlr4+/+ mice; #P < 0.05; DT-pLIVE-S100A9 RIP-DTR; Tlr4−/− mice vs. DT-treated pLIVE RIP-DTR; Tlr4+/+ mice. Circulating glucose j and β-hydroxybutyrate k content in DT-treated RIP-DTR; Tlr4−/− (n = 7) and RIP-DTR; Tlr4+/+ (n = 6) mice after icv leptin therapy. Statistical analysis in k was done using a two-tailed unpaired Student’s t-test. Source data are provided as a Source Data file
