Fig. 1. Utx^Ksp KO mouse was resistant to HFD-induced obesity.

a Representative images of renal UTX staining of human subjects, n = 4 or five independent subjects with control or obesity, respectively. Scale bar, 50 μm. Brown color indicates positive staining. b Representative images of UTX (red)/LTL (lotus tetragonolobus lectin, detecting proximal tubules; green), UTX (red)/PNA (peanut agglutinin, detecting distal tubules and collecting ducts; green), UTX (green)/α-SMA (alpha-smooth muscle actin, mesangial cell marker; red), and UTX (green)/WT1 (Wilms’ tumor 1, podocyte marker; red) staining on the renal sections of WT (n = 6) and HFD (n = 4) mice. DAPI staining shown in blue. Scale bar, 100 μm. c Genotyping of WT and Utx^Ksp KO mice. d Western blots of UTX, α-tubulin, H3K27me3 and H3 in renal medulla (left, n = 4) and cortex (right, n = 6) of WT and Utx^Ksp KO mice. e qPCR results of Utx in renal medulla (R med.), renal cortex (R cor.), liver and BAT of WT and Utx^Ksp KO mice. n = 6 independent animals (mean ± SD); ^***P_{R med}. < 0.0001, ^***P_{R cor}. < 0.0001 ₍unpaired, two-tailed t-test). f Representative images of UTX (red)/LTL (green), UTX (red)/PNA (green) staining on the renal sections of HFD-fed WT and Utx^Ksp KO mice. DAPI (blue) stained nuclei. Scale bar, 100 μm, n = 4 independent animals. g–i, Growth curves (g), body mass (h), and gross view (i) of WT and Utx^Ksp KO mice. g n = 8, 5 independent animals for WT + HFD or Utx^Ksp KO + HFD group, respectively (mean ± SD), ^**P_{body weight} or ^***P_{body weight} from 0.0035 to 0.0007; unpaired, two-tailed t-test; h n = 6, 6, 8, five independent animals for WT + NC or Utx^Ksp KO + NC or WT + HFD or Utx^Ksp KO + HFD group, respectively (mean ± SD), ^***P_{Fat (WT+NC vs WT+HFD)} < 0.0001, ^***P_{Fat (WT+HFD vs Utx}^Ksp _KO+HFD) < 0.0001; ^***P_{Lean (WT+NC vs WT+HFD)} < 0.0001, ^***P_{Lean (WT+HFD vs Utx}^Ksp _{KO +HFD)} < 0.0001 (one-way ANOVA). j–l Serum levels of TG (j, left), cholesterol (j, right), insulin (k, left), leptin (k, right) and non-fasting blood glucose (l) of WT and Utx^Ksp KO mice, n = 6, 6, 8, 5 independent animals for WT + NC or Utx^Ksp KO + NC or WT + HFD or Utx^Ksp KO + HFD group, respectively (mean ± SD); ^***P_{TG (WT+NC vs WT+HFD)} < 0.0001, ^***P_{TG (WT+HFD vs Utx}^Ksp _KO+HFD) < 0.0001; ^***P_{cholesterol (WT+NC vs WT+HFD)} < 0.0001, ^***P_{cholesterol (WT+HFD vs Utx}^Ksp _KO+HFD) < 0.0001; ^*P_{Insulin (WT+NC vs WT+HFD)} = 0.0294, ^*P_{Insulin (WT+HFD vs Utx}^Ksp _KO+HFD) = 0.0378; ^***P_{Leptin (WT+NC vs WT+HFD)} < 0.0001, ^***P_{Leptin (WT+HFD vs Utx}^Ksp _KO+HFD) < 0.0001; ^**P_{glucose (WT+NC vs WT+HFD)} = 0.0027 (one-way ANOVA). m, n GTT (m) and ITT (n) results of WT and Utx^Ksp KO mice. m n = 4, five independent animals for WT + HFD or Utx^Ksp KO + HFD group, respectively (mean ± SD), ^*P_GTT(0) = 0.0214; ^*P _GTT(60) = 0.0373; ^***P _GTT(90) = 0.0003, ^*P_GTT(120) = 0.0428; (n) n = 8, five independent animals for WT + HFD or Utx^Ksp KO + HFD group, respectively (mean ± SD), ^**P_ITT(15) = 0.0063, ^**P_ITT(30) = 0.0011, ^***P _ITT(45) = 0.0009, ^*P _ITT(60) = 0.0238, ^*P _ITT(90) = 0.0341, ^*P _ITT(120) = 0.0125, unpaired, two-tailed t-test. Source data are provided in the Source Data file.