Fig. 6: IR-61 triggers weight loss and improves insulin sensitivity in obese mice.

a Body weight of mice on NCD or HFD concurrently treated with IR-61 or vehicle control. b Body weight of the mice with established obesity treated with IR-61 or vehicle control. c Fat distribution was detected by μCT. Yellow indicates visceral fat and red indicates subcutaneous fat. d–f VO₂, VCO₂, and heat production over a 24-h period of obese mice treated with IR-61 or vehicle control for 2 weeks were obtained by indirect calorimetry. The average VO₂, VCO₂, and heat production of each mouse represented as scatterplots. g GTT and ITT were performed in HFD-fed mice treated preventatively with IR-61 or vehicle control for 15 weeks. Area under the curve (AUC) was determined for each individual animal for GTT and ITT. h GTT and ITT on established obesity mice treated with IR-61 or vehicle control for 6 weeks. The AUC was determined for each individual animal for GTT and ITT. i Acute insulin signaling in the epi WAT, soleus and liver of mice on HFD. j GTT and ITT on the established obesity mice treated with vehicle, IR-61, BMS-303141, and BMS-303141+IR-61 for 2 weeks. The AUC was determined for each individual animal for GTT and ITT. Sample sizes are (a) n = 7/7/7/7 mice, (b) n = 7/7 mice, (d–f) n = 11/11 mice, (g, h) n = 7/7 mice, (i) representative western blot of n = 2 vehicle + PBS, n = 3 vehicle + insulin, n = 2 IR-61 + PBS, n = 3 IR-61 + insulin mice and quantification of p-Akt/Akt in n = 3 vehicle + insulin and IR-61 + insulin mice, (j) n = 5/5/5/5 mice. Data are presented as the mean ± SEM (*p < 0.05, **p < 0.01, ***p < 0.001; two-way ANOVA with Bonferroni post hoc test; longitudinal data in panels (a, b, d–h, j)) or two-sided Student’s t-test (plot graphs in panels (d–j)). Exact p-values are given in the Source Data file. Source data are provided as a Source Data file.