(A) BW curve on Rosi treatment. Mice were rendered insulin resistant after 16 weeks of HFD feeding (started at 6 weeks old), then switched to a HFD containing Rosi. *P < 0.05 for female WT vs. female 2KR by 2-tailed t test. n = 8 male WT; n = 8 male 2KR; n = 7 female WT; n = 8 female 2KR. (B) Body composition of male mice on Rosi treatment for 10 weeks. Rosi treatment started at 8 weeks of HFD feeding. *P < 0.05; **P < 0.01 for WT vs. 2KR by 2-tailed t test. n = 8 WT; n = 8 2KR. (C) WAT fat pad sizes in male mice on 15-week Rosi treatment. Mice were sacrificed after overnight fasting followed by 4 hours of refeeding. *P < 0.05 for WT vs. 2KR by 2-tailed t test. n = 8 WT; n = 8 2KR. (D and E) ipGTT (D) and AUC (E) before and after 2 weeks of Rosi treatment in BW-matched DIO male mice. n = 7 WT; n = 6 2KR. (F) Fasting blood glucose levels in male mice after 16 weeks on Rosi treatment. n = 7 WT (vehicle [veh]); n = 7 2KR (vehicle); n = 8 WT (Rosi); n = 8 2KR (Rosi). (G and H) ITT (G) and AUC (H) in male mice at 18 weeks on Rosi treatment. n = 7 WT (vehicle); n = 7 2KR (vehicle); n = 8 WT (Rosi); n = 8 2KR (Rosi). (I) Plasma insulin levels in male mice after 18 weeks on Rosi treatment. n = 7 WT (vehicle); n = 7 2KR (vehicle); n = 8 WT (Rosi); n = 8 2KR (Rosi). (J and L) Liver size (J), histological analysis by H&E staining (K), and hepatic TG content (L) in male mice after 24 weeks of Rosi treatment. Mice were sacrificed after overnight fasting. Original magnification, ×100. n = 7 WT (vehicle); n = 7 2KR (vehicle); n = 8 WT (Rosi); n = 8 2KR (Rosi). In D–L, effects of 2KR (*P < 0.05; **P < 0.01, WT vs. 2KR) and Rosi (#P < 0.05; ##P < 0.01, vehicle vs. Rosi) by 2-way ANOVA. In F–L, n = 7 WT (vehicle); n = 7 2KR (vehicle); n = 8 WT (Rosi); n = 8 2KR (Rosi). Data represent mean ± SEM.