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. Author manuscript; available in PMC: 2020 Apr 15.
Published in final edited form as: Nat Med. 2019 Mar 4;25(4):575–582. doi: 10.1038/s41591-019-0358-x

Figure 2. IL1R1 is required for celastrol’s anti-obesity effects.

Figure 2.

Il1r1+/+ and Il1r1−/− mice were fed a HFD for 20 weeks and treated with vehicle (Veh) or celastrol (Cel, 100 μg/kg, i.p., once a day) for 3 weeks. n=9 for vehicle- or celastrol-treated Il1r1+/+ mice; n=12 for vehicle- and n=13 for celastrol-treated Il1r1−/− mice. (a) Body weight. Cel vs. Veh, P<0.0001 for Il1r1+/+ mice and P=0.653 for Il1r1−/− mice. (b) Percent change in body weight of Il1r1+/+ and Il1r1−/− mice during the treatment period. Cel vs. Veh, P<0.0001 for Il1r1+/+ mice and P=0.104 for Il1r1−/− mice. (c) Average 24-hour food intake per mouse during the first week of vehicle or celastrol treatment. Cel vs. Veh, P<0.0001 for Il1r1+/+ mice and P=0.9 for Il1r1−/− mice. (d-f) DEXA of Il1r1+/+ and Il1r1−/− mice treated with vehicle or celastrol for 3 weeks. (d) Lean body mass. (e) Fat mass. Cel vs. Veh, P=0.005 for Il1r1+/+ mice and P>0.99 for Il1r1−/− mice. (f) Fat % at the end of the treatment period. Cel vs. Veh, P=0.0005 for Il1r1+/+ mice and P=0.175 for Il1r1−/− mice. (g) Plasma leptin levels in Il1r1+/+ and Il1r1−/− mice after 3 weeks of vehicle or celastrol treatment. Cel vs. Veh, P<0.0001 for Il1r1+/+ mice and P=0.162 for Il1r1−/− mice. (h) GTT after 1 week of vehicle or celastrol treatment and (i) AUC analysis of GTT. Cel vs. Veh, P<0.0001 for Il1r1+/+ mice and P=0.811 for Il1r1−/− mice. (j) ITT after 2 weeks of treatment and (k) AUC analysis of ITT. Cel vs. Veh, P<0.0001 for Il1r1+/+ mice and P=0.634 for Il1r1−/− mice. (l) Six-hour fasting blood glucose of Il1r1+/+ and Il1r1−/− mice after 1 week of vehicle or celastrol treatment. Cel vs. Veh, P<0.0001 for Il1r1+/+ mice and P=0.88 for Il1r1−/− mice. (m) Plasma insulin levels of Il1r1+/+ mice and Il1r1−/− mice after 3 weeks treatment. Cel vs. Veh, P=0.04 for Il1r1+/+ mice and P>0.99 for Il1r1−/− mice. (n) Plasma AST after 3 weeks of celastrol treatment. Cel vs. Veh, P=0.04 for Il1r1+/+ mice and P>0.99 in Il1r1−/− mice. (o) Plasma ALT after 3 weeks of celastrol treatment. Cel vs. Veh, P=0.02 for Il1r1+/+ mice and P>0.99 for Il1r1−/− mice. (p) H&E staining of liver sections from Il1r1+/+ and Il1r1−/− mice treated with vehicle or celastrol for 3 weeks. The experiments were repeated in two independent cohorts with similar outcomes (total n=14 for vehicle- or celastrol-treated Il1r1+/+ mice; n=17 for vehicle- and n=19 for celastrol-treated Il1r1−/− mice). Values indicate average ± s.e.m. P values were determined by two-way ANOVA with Bonferroni’s multiple comparisons test. * P < 0.05, ** P < 0.01, *** P < 0.001, n.s., not significant (P>0.05).