Fig. 3: ANT2 AKO mice are protected from HFD-induced adipose tissue inflammation, glucose intolerance and insulin resistance.

a, Glucose tolerance tests (GTTs) in NCD mice (WT, n = 10; ANT2 AKO, n = 5). b, Fasting plasma insulin levels in NCD mice (n = 11 and 6 mice for WT and ANT2 AKO, respectively). c, GTTs in mice fed HFD for 12 weeks (n = 11 and 8 mice for WT and ANT2 AKO, respectively). ^aP = 0.008, ^bP = 0.043 and ^cP = 0.028, according to two-way ANOVA with post-hoc two-tailed t-tests between individual groups. d, Fasting plasma insulin levels in HFD mice (n = 8 and 11 mice for WT and ANT2 AKO, respectively). e, Insulin tolerance tests (ITTs) in mice fed HFD for 12 weeks (n = 8 and 11 mice for WT and ANT2 AKO, respectively). ^aP = 0.020, ^bP = 0.002, ^cP = 0.030, ^dP = 0.005 and ^eP = 0.005 according to two-way ANOVA with post-hoc two-tailed t-tests between individual groups. f–j, Systemic and tissue-specific effects of ANT2 AKO were determined by hyperinsulinemic euglycemic clamp studies in mice fed HFD for 12 weeks (n = 4 and 6 mice for WT and ANT2 AKO, respectively). Glucose infusion rate (GIR) (f). Hepatic glucose production (HGP) (g). Hepatic glucose production suppression (h). Suppression of plasma FFA levels (i). Insulin-stimulated glucose disposal rate (j). k, Akt phosphorylation (p-AKT) in eWAT, liver, and muscle of WT and ANT2 AKO mice. Representative data from two independent experiments are shown. l, mRNA levels of adiponectin in eWAT and primary adipocytes of HFD WT and ANT2 AKO mice (n = 8 mice per group). *P = 0.027, ^ξP = 0.018. m,n, Western blot analysis of adiponectin protein levels in eWAT (m; n = 12 mice per group) and serum (n; n = 10 and 11 for WT and AKO, respectively) of HFD WT and ANT2 AKO. Representative images are on top of each bar graph. o,p, mRNA levels of inflammatory cytokines in primary adipocytes (o) or eWAT (p) of HFD WT (n = 16 mice) and ANT2 AKO (n = 10 mice per group) mice. q, Serum levels of PAI-1 and MCP-1 in HFD WT (n = 11 mice) and ANT2 AKO mice (n = 15 mice). Statistical analyses in d,f–i,l–q were performed by two-tailed Student’s t-test. All data are presented as mean ± s.e.m.