Fig. 7.

Increased hepatic epoxide:diol is conserved during MASLD. (a) sEH surrogate 14,15-EET:DHET in liver biopsies stratified according to patients with obesity (N = 22) and patients with obesity and T2DM (N = 11) or MASH [NAS scoring, 0–2 no MASLD (N = 17), 3–4 intermediate/MASLD/MASH (N = 13), 5+ MASH (N = 3)] or ballooning score (0–2; score 0: N = 12, score 1: N = 8, score 2: N = 13) or steatosis score (0–3; score 0: N = 22, score 1: N = 8, score 2: N = 3, score 3: N = 0). (b) Correlation of sEH surrogates, measured in each tissue (liver, plasma, WAT) by UPLC-MS/MS with markers of MASLD, measured by machine learning (See Methods; CPA%, ballooning%, fat%, inflammation %) for each liver biopsy (N = 35). Grey highlights denote significant associations. (c) Schematic summary of CYP-sEH pathway evolution between lean and obese states in the WAT and during WAT inflammation and hepatic steatosis. Significance was tested by student's t-test (2-sided) (a), Kruskal–Wallis followed by Dunn's multiple comparison (a) and Spearman's correlation coefficient (b).