Fig. 1: Acod1 deficiency protects mice from diet-induced obesity.
A qPCR analysis of Acod1 mRNA levels in the indicated tissues from WT and Acod1-/- mice fed with ND (n = 4) or HFD (n = 6) for 16 weeks. Data as mean ± sem from one experiment out of two independently executed. B Itaconate levels in indicated tissues from mice as described in A; ND (n = 4), HFD-WT (n = 6), HFD-Acod1-/- (n = 4). Data as mean ± sem from one experiment out of two independently executed. C ACOD1 mRNA levels (GSE158237) in colon of healthy (BMI < 25 kg/m2, n = 13) and obese subjects (BMI > 30 kg/m2, n = 16). Boxes extend from 25th to 75th percentiles, black lines = median, whiskers=minimum to maximum. D Correlation analysis between colonic ACOD1 mRNA (GSE158237) and relative changes in plasma glucose levels measured 2 h after oral glucose overload (OGTT) compared with baseline, in human subjects described in Fig. 1C. r = Pearson’s correlation coefficient. E Body weights of mice as described in A. Data as mean ± sem of n = 17 (ND-WT), n = 18 (ND- Acod1-/-), n = 26 (HFD-WT) and n = 22 (HFD-Acod1-/-) from three experiments independently executed. F Representative images of WT and Acod1-/- mice after HFD. G Weights (g) of the indicated tissues from mice treated as in A at the end of the experiment; ND (n = 6), HFD-WT (n = 7), HFD-Acod1-/- (n = 6). Data as mean ± sem from one representative experiment out of three independently executed. Representative images of H&E staining of iWAT, eWAT, pWAT (H) and BAT (I) from HFD-fed WT and Acod1-/- mice. J Fasting glycemia of mice treated as in A; ND (n = 6), HFD (n = 7). Data as mean ± sem from one representative experiment out of two independently executed. K Fasting insulinemia of in mice treated as in A; ND (n = 4), HFD-WT (n = 7), HFD-Acod1-/- (n = 6). Data as mean ± sem from one representative experiment out of two independently executed. L Glucose tolerance test (GTT) in mice treated as in A; ND (n = 6), HFD (n = 7). Data as mean ± sem from one representative experiment out of two independently executed. M Insulin tolerance test (ITT) in mice described in A; ND (n = 5), HFD (n = 7). Data as mean ± sem from one representative experiment out of two independently executed. In: (A–C, G): t-test; (D) Pearson correlation; (E), (L), and (M) two-way ANOVA; (J-K), one-way ANOVA with Dunnett’s multiple comparisons test compared to HFD-fed WT mice. *P < 0.05; **P < 0.01; ***P < 0.001; ns not significant.
