Extended Data Fig. 2: Effects of longer SGLT2 inhibition on senescent cells in visceral adipose tissue.
From: SGLT2 inhibition eliminates senescent cells and alleviates pathological aging
a, Protocol of the experiments to test the senolytic effects of 4 weeks of treatment with canagliflozin (Cana). NC, normal chow; HFD, high-fat diet. b, Body weight and weight of gonadal white adipose tissue (gWAT) and inguinal WAT (iWAT) in mice fed NC or HFD with or without canagliflozin (n = 5 each). c, SA-β-gal activity (n = 9 each) and hematoxylin and eosin (HE) staining (n = 3 each) in gWAT of mice as prepared in Extended Data Fig. 2b. d, FACS analysis for SPiDERβ-gal + cells in gWAT of mice as prepared in Extended Data Fig. 2b (n = 4, 5, 6). e, Glucose tolerance test (n = 6 each) and insulin tolerance test (n = 5, 5, 6) of mice as prepared in Extended Data Fig. 2b. f, Western blot analysis for p53 in gWAT of mice as prepared in Extended Data Fig. 2b (n = 9, 9, 8 from 3 gels/blots processed in parallel). g, qPCR analysis for Cdkn1a, Cdkn2a, Tnf, and Ccl2 in gWAT of mice as prepared in Extended Data Fig. 2b (n = 13,15,15). 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) (b–g) or repeated measures analysis (e). *P < 0.05, **P < 0.01. Exact P-value: NC versus HFD: 0.0003 (Body weight), 0.0053 (gWAT weight) and < 0.0001 (iWAT weight), NC versus HFD+Cana: 0.001 (Body weight), 0.0002 (gWAT weight) and < 0.0001 (iWAT weight) (b); NC versus HFD: 0.0016 (SA-β-gal activity) and 0.0004 (Crown-like structure count), HFD versus HFD+Cana: 0.0071 (SA-β-gal activity) and 0.0031 (Crown-like structure count) (c); NC versus HFD: 0.0219, HFD versus HFD+Cana: 0.0119 (d); NC versus HFD: < 0.0001 (GTT-trend, ITT-trend, and ITT-AUC) and 0.0002 (GTT-AUC), HFD versus HFD+Cana: < 0.0001 (GTT-trend), 0.0002 (GTT-AUC), 0.0013 (ITT-trend) and 0.0228 (ITT-AUC) (e); NC versus HFD: < 0.0001, HFD versus HFD+Cana: 0.039 (f); NC versus HFD: 0.0228(Cdkn1a) and < 0.0001 (Cdkn2a, Ccl2, and Tnf), HFD versus HFD+Cana: 0.0122 (Cdkn1a), 0.0075 (Cdkn2a), < 0.0001 (Ccl2) and 0.013 (Tnf) (g). Data are shown as the mean ± SE in plots of all individual data (b–g) or as the mean ± SE in the spaghetti plot shown in Supplementary Fig. 1 (e). Gating strategy in FACS analysis was shown in Supplementary Fig. 3c (d).