Extended Data Fig. 2: IL1R1 deficiency leads to significantly higher levels of obesity.
From: IL1R1 is required for celastrol’s leptin-sensitization and antiobesity effects
Il1r1–/– mice and their wild-type (Il1r1+/+) littermates were fed a HFD for 16 weeks to induce obesity. The experiments were repeated two times with similar results. a, PCR analysis of the Il1r1 locus in genomic DNA from Il1r1+/+ and Il1r1–/– mice. b,c, qPCR analysis of Il1r1 mRNA levels in the hypothalamus (P < 0.0001) (b), and liver (P = 0.007) (c). n = 6 for the Il1r1+/+ group and n = 4 for the Il1r1–/– group. d, Body weights of Il1r1+/+ and Il1r1–/– mice during HFD feeding (n = 10 mice for the Il1r1+/+ group and n = 9 mice for the Il1r1–/– group; P < 0.0001). e, Average 24-h food intake per mouse after 4, 8, 12, or 16 weeks of HFD feeding (n = 3 cages for each group). f–h, DEXA analysis of body composition after 16 weeks of HFD (n = 10 mice for the Il1r1+/+ group and n = 9 mice for the Il1r1–/– group), including lean mass (P = 0.163) (f), fat mass (P = 0.003) (g), and fat percentage (P = 0.001) (h). i, Plasma leptin levels of Il1r1+/+ and Il1r1–/– mice at 4, 8, 12, and 16 weeks of HFD feeding (n = 5 mice for each group; 4 weeks, P = 0.001; 8 weeks, P = 0.02). j,k, Blood glucose levels of Il1r1+/+ and Il1r1–/– mice during GTT performed after 10 weeks on the HFD (j) and AUC analysis of GTT results (n = 10 mice for the Il1r1+/+ group and n = 9 mice for the Il1r1–/– group; P = 0.03) (k). l,m, Blood glucose levels of Il1r1+/+ and Il1r1–/– mice during ITT performed after 12 weeks on HFD feeding (l) and AUC analysis of ITT results (n = 10 mice for the Il1r1+/+ group and n = 9 mice for the Il1r1–/– group; P = 0.007) (m). n, Fifteen-hour fasting blood glucose levels of Il1r1+/+ and Il1r1–/– mice after 10 weeks of HFD feeding (n = 10 mice for the Il1r1+/+ group and n = 9 mice for the Il1r1–/– group; P = 0.03). o, Six-hour fasting blood glucose levels of Il1r1+/+ and Il1r1–/– mice after 12 weeks on HFD feeding (n = 10 mice for the Il1r1+/+ group and n = 9 mice for the Il1r1–/– group; P = 0.003). p, Plasma insulin levels in Il1r1+/+ and Il1r1–/– mice after 4, 8, 12, or 16 weeks on HFD feeding (n = 5 mice for the Il1r1+/+ group and n = 4 mice for the Il1r1–/– group; 4 weeks, P = 0.007; 8 weeks, P = 0.184). Values indicate averages ± s.e.m. P values were determined by two-way ANOVA with Bonferroni’s multiple-comparisons test (d,j,l) or two-tailed Student’s t test (b,c,e–i,k,m–p). *P < 0.05, **P < 0.01, ***P < 0.001; n.s., not significant (P > 0.05).
