Extended Data Fig. 1: Obesity reduces AT PEPD activity and promotes PEPD release in association with AT fibrosis and insulin resistance.

a, Age, BMI, glycaemic and lipidic status in the different human cohorts. b, PEPD serum/ScW levels, BMI and metabolic parameters in obese subjects from cohort cohort 2e (n = 9) with low vs. high VsW PEPD levels. c, PEPD activity/ecplants levels, BMI, blood chemistry parameters and liver Actitest score in obese subjects (cohort 2e,f) with high (>2.065 nmol pro/mg prot/min) vs. low (<2.065 nmol pro/mg prot/min) PEPD peptidase activity in VsW. d, Area under the receiver operating curve (AUC) values (95% CI) for VsW and ScW PEPD peptidase activity (PA) to discriminate subjects with type 2 diabetes (cohort 2e,f).e, Pearson correlation between PEPD serum levels and, ScW and VsW ECM remodelling markers and metabolic parameters in obese subjects from cohort 2b (n = 14 biologically independent samples). f, g, Pepd mRNA relative expression (f), and PEPD prolidase activity (g) in ScW, GnW and liver from C57Bl/6 mice in chow (n = 6) and 58% HFD (n = 8, 20 weeks) conditions.* compared to chow diet. h, ELISA analysis of PEPD protein in serum from C57/Bl6 mice fed chow (n = 6) or 20 weeks 58% HFD (n = 8). I-k. ScW prolidase activity (i), PEPD serum level (j) and ScW peri-ad collagen in C57Bl/6 mice fed 2, 8, 16 or 28 weeks (n = 8/group) with chow diet (ch) of HFD 45% (HF). l, Prolidase activity in the serum of C57Bl6 mice fed chow (2, 28 weeks) or HFD 58% (28 weeks). m, Pearson correlation matrix between ScW and GnW ECM remodelling markers and metabolic parameters in chow and HFD conditions (n = 22). Data presented as mean values +/− SEM. Data was analysed using a two-tailed Student’s t-test (b, c, h) or a 2-way ANOVA followed by a Sidak post-hoc multiple comparisons test (f, g, i-k).