Extended Data Fig. 2: PEPD pharmacological inhibition promotes AT fibro-inflammation independently from obesity.

a-d. ALAT and ASAT serum levels (a), body weight (b), and fat mass % (c), and tissue weight (d) in mice treated 10 weeks or not (control) with CBZ-Pro (n = 8 biologically independent animals per group). e, f. Fasting insulin and FFA blood levels from CBZ-Pro-treated mice compared to control mice (n = 8 biologically independent animals per group) fed chow and HFD 58% for 16 weeks. g. Fasting insulin blood level before and 30 min after glucose injection (2 g/kg) in CBZ-Pro-treated mice compared to controls (n = 8 biologically independent animals per group). h,i. Representative images of blots and quantification of total and basal phosphorylated (Ser473) AKT in GnW (h) and gastrocnemius muscle (i) of CBZ-Pro- treated mice compared to controls (n = 8 biologically independent animals per group). j. Heat map representing the four factors extracted through exploratory factor analysis. The columns report the factors loadings of the observed variables. k. Representative images of red Sirius staining in ScW and GnW of control and CBZ-Pro treated mice (n = 8 biologically independent animals per group) fed HFD 58%, and corresponding quantification of peri-adipocyte collagen content (peri-AD) represented in % Area (excluding perivascular staining). l, m. Blood glucose levels up to 120 min. after an intraperitoneal injection of glucose (2 g/kg) in a glucose tolerance test (l) or insulin (0.75 IU/kg) in an insulin tolerance test (m) in control and CBZ-Pro treated mice (n = 8 biologically independent animals per group) fed HFD 58%. Respective AUC are represented. Data is presented as mean values +/− SEM. Data was analysed using a two-tailed Student’s t-test (a-d, h, i l, m) or a 2-way ANOVA followed by a Turkey (e-g) or Sidak (k-m) post-hoc multiple comparisons test.