Fig. 3: Ido1 deficiency in adipocytes renders the mice with decreased Kyn level and resistance to obesity.

a Based on the CRISPR-Cas9 system, the Ido1^flox/flox mice were generated by inserting two loxP sequences in the same direction into the intron flanking exon 4 of IDO1, which would generate a stop codon in exon 3 to produce a nonfunctional IDO1 protein after Cre-mediated gene deletion. The Ido1^flox/flox mice were crossed with the Adipoq-CreER^T2 mice to get the Adipq-CreER^T2-Ido1^flox/flox mice. After intraperitoneally injected with tamoxifen (75 mg/kg/d) for 5 days, the Ido1-aKO mice and their littermates were employed for following studies. b Body weights of Ctrl and Ido1-aKO mice fed with HFD for 12 weeks (n = 8). Kyn, Trp concentration and KTR in eWAT (c) and plasma (d) from Ctrl and Ido1-aKO mice fed with HFD for 12 weeks (n = 8). e Respiratory exchange ratio (left) and heat production (right) of HFD-fed Ctrl and Ido1-aKO mice (n = 4). f Representative images of ¹⁸F-FDG micro-PET/CT (left) and quantification (right) of tissue FDG uptake in Ctrl and Ido1-aKO mice fed with HFD for 12 weeks (SUV_muscle was used as a standardized value) (n = 3). GTT (g) and ITT (h) of Ctrl and Ido1-aKO mice fed with HFD for 12 weeks (left) and areas under curves (AUC) (right) (n = 8). i Plasma insulin levels of the Ctrl and Ido1-aKO mice (n = 8). j Western blot analysis of p-AKT^Ser473 and AKT, in eWAT from Ctrl and Ido1-aKO mice fed with 12-week HFD (n = 4). k Flow cytometry analysis of macrophage subsets in the eWAT of Ctrl mice and Ido1-aKO mice (n = 8). Data were represented as mean ± SEM. RER in e was analyzed by the moving average. Student’s t test was used for statistical analysis. Statistical significance was assessed by two-way ANOVA followed with Bonferroni’s multiple comparisons test (b, e, g and h), two-sided Student’s t test (c, d, f, i–k) and significant differences were indicated with p values. Source data are provided in the Source Data file.