Extended Data Fig. 1: Effects of SGLT2 inhibition on senescent cells in visceral adipose tissue.

a, Food intake of mice prepared according to the experimental protocol shown in Fig. 1a (n = 6 each). b, Oxygen consumption (VO2), CO2 emission (VCO2), and respiratory exchange ratio (RER) of mice as prepared in Extended Data Fig. 1a (n = 5, 6, 5). c, Protocol for performing the glucose tolerance test (GTT) and insulin tolerance test (ITT) after 1 week of canagliflozin administration followed by 1 week of no canagliflozin administration. NC, normal chow; HFD, high-fat diet. d, Glucose tolerance test (GTT) and insulin tolerance test (ITT) of mice as prepared in Extended Data Fig. 1c (n = 5 each). WO, wash out. e, SA-β-gal activity in gonadal white adipose tissue (gWAT) of mice as prepared in Extended Data Fig. 1c (n = 5 each). f, Immunostaining for p53 in gWAT as prepared in Extended Data Fig. 1a (n = 4, 3, 4). g, qPCR analysis for Cdkn1a and Cdkn2a in multiple organs of mice as prepared in Extended Data Fig. 1a (Liver, n = 6 each; Muscle, n = 5 each). h, ELISA for CCL2 (n = 11, 12, 11) and TNFα (n = 10, 12, 12) in the blood of mice as prepared in Extended Data Fig. 1a. i, RNA-sequence analysis for inflammatory molecules in gWAT of mice as prepared in Extended Data Fig. 1a (n = 2 each). Data were analyzed by two-way ANOVA followed by Tukey’s multiple comparison test (for equal variance) or Dunnett’s multiple comparison test (for unequal variance) (a, b, d–h). *P < 0.05, **P < 0.01. Exact P-value: NC versus HFD: 0.0003 (Food intake) and < 0.0001 (Water intake), NC versus HFD+Cana: < 0.0001 (Food intake and Water intake), HFD versus HFD+Cana: 0.008 (Water intake) (a); NC versus HFD: 0.0003 (VCO2-light and VCO2-24 hr), 0.0004 (VCO2-dark), 0.0006 (RER-light and RER-dark) and 0.0005 (RER-24 hr), NC versus HFD+Cana: 0.0003 (VCO2-light), 0.0007 (VCO2-dark), 0.0001 (VCO2-24 hr), < 0.0001 (RER-light, RER-dark and RER-24 hr) (b); NC versus HFD: < 0.0001 (GTT-trend, GTT-AUC, ITT-trend and ITT-AUC), HFD versus HFD+Cana(WO): 0.0086 (GTT-trend), 0.0029 (GTT-AUC), < 0.0001 (ITT-trend), 0.0004 (ITT-AUC) (d); NC versus HFD: < 0.0001, HFD versus HFD+Cana(WO): 0.0035 (e); NC versus HFD: 0.003, HFD versus HFD+Cana(WO): 0.0291 (f); NC versus HFD: 0.0122 (Liver-Cdkn2a) and 0.0017 (Liver-Cdkn1a), HFD versus HFD+Cana: 0.0097 (Liver-Cdkn2a) and 0.0003 (Liver-Cdkn1a) (g); NC versus HFD: 0.0009 (CCL2), HFD versus HFD+Cana: 0.0575 (CCL2) (h). Data are shown as the mean ± SE in plots of all individual data (a, b, d–h) or as the mean ± SE in the spaghetti plot shown in Supplementary Fig. 1 (d).

Source data