Figure 1.

Succinate levels are elevated in the active phase of Crohn’s disease and correlate positively with UCP1 gene expression in pre-adipocytes. [A] Circulating succinate plasma levels in controls [healthy subjects] [n = 10] and in patients with active [n = 17] or inactive [n = 12] Crohn’s disease [CD]. Differences were analysed with the Kruskal–Wallis test with post hoc Dunn’s multiple comparison test. *p < 0.0001 vs. control; ^$p < 0.05 vs. active CD. [B] Positive correlation between plasma succinate and high-sensitivity C-reactive protein [hsCRP] levels. [C] SUCNR1 expression in subcutaneous [SAT] and [D] visceral [VAT] adipose tissue [n = 8 per group], and in [E] VAT-derived adipose tissue macrophages [ATMs] [n = 5 per group] and [F] VAT-derived stem cells [ASCs] [n = 8 per group]. [G] Positive correlation between visceral-ASC SUCNR1 mRNA and circulating succinate. [H] Succinate treatment differentially affects adipose tissue of patients with CD according to clinical status. Quantitative PCR analysis of pro-inflammatory genes in VAT explants, unstimulated or stimulated with succinate [250 µM] for 24 h, from controls and from patients with active or inactive CD [n = 4 per group]. [I] Succinate release in 24-h-conditioned medium of VAT explants from controls and from patients with active or inactive CD [n = 4 per group]. [J] UCP1 expression in ASCs from controls and from patients with active or inactive CD after succinate treatment. [K] Serum from patients with active CD [which has a high amount of succinate] increases UCP1 gene expression in ASCs isolated from controls. [L] Positive correlation between UCP1 expression in ASCs and plasma succinate levels. Pearson’s correlation coefficient with Bonferroni adjustment was used to analyse the relationship between parameters. *p < 0.05 vs. control; ^$p < 0.05 as indicated in the figure.