Fig 2: Effects of TPE-CA on the CYPs epoxygenase and CYP hydroxylase signal transduction of AA metabolism. (A) The relative expression of NOX2, CYP2C11, sEH, CYP4A and eNOS. (B) The concentration of ACE. (C) The concentration of 14, 15-EET. (D) The concentration of 20-HETE. #p<0.05 vs Normal group, ##p<0.01 vs Normal group, ###p<0.001 vs Normal group. *p<0.05 vs H-Met group, **p<0.01 vs H-Met group, ***p<0.001 vs H-Met group.

Fig 3: Cytochrome P450-EPHX pathway regulates IL-10 secretion from autophagy-deficient adipose tissues upon DSS-induced intestinal inflammation Quantification of Il10 transcript levels in RAW264.7 upon stimulation to epoxy fatty acids (n = 3/group).Quantification of IL-10 protein levels in the supernatant of RAW264.7 upon stimulation to epoxy fatty acids (n = 3/group).Quantification of IL-10 protein levels in the supernatant of ex vivo cultured adipose tissues from water- or DSS-treated wild-type mice in the absence or presence of the cytochrome P450 inhibitor 1-ABT (n = 5–9/group).Quantification of IL-10 protein levels in the supernatant of ex vivo cultured adipose tissues from DSS-induced Atg7 Ad mice in the absence or presence of the EPHX1 inhibitor NTPA and EPHX2 inhibitor TPPU (n = 4/group). Dotted line represents IL-10 secretion from adipose tissues of DSS-induced wild-type mice.Graphical summary of the anti-inflammatory fat-gut crosstalk during intestinal inflammation. Designed using BioRender. Data are represented as mean ± s.e.m. (A, B) One-Way ANOVA. (C, D) Paired Student's t-test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Source data are available online for this figure.

Fig 4: Adipocyte autophagy loss activates NRF2-EPHX1 pathway and alters intratissual oxylipin balance Differential gene expression in visceral adipocytes from water-treated WT and Atg7 Ad animals 2 weeks after tamoxifen treatment.Differential gene expression in visceral adipocytes from DSS-treated WT and Atg7 Ad animals on day 7 post-DSS treatment.Venn diagram of commonly regulated genes between Atg7-deficient and Atg7-sufficient adipocytes during water or DSS treatment.GSEA enrichment analysis between Atg7-deficient and Atg7-sufficient adipocytes during DSS treatment.Fold change expression of NRF2-target genes in primary visceral adipocytes on day 7 after DSS induction from normalized counts of RNAseq dataset (n = 6/group).Representative immunoblot for NRF2 protein expression and quantification (n = 16–18/group).Transcriptional expression of Ephx1 and Ephx2 in visceral adipocytes on day 7 after DSS induction (n = 20–25/group).Representative immunoblot of EPHX1 and EPHX2 in gonadal adipose tissues on day 7 after DSS induction. Asterix indicating nonspecific band (n = 14–18/group).Schematic overview of cytochrome P450-EPHX oxylipin pathway.Normalized fold change differences in epoxy fatty acid precursor fatty acids, docosahexaenoic acid (DHA), arachidonic acid (AA), and linoleic acid (LA) in mWAT and gWAT (n = 13–14/group).Normalized ratios of epoxy fatty acid to their corresponding diol fatty acid pairs in mWAT and gWAT (n = 6–8/group). Data are represented as mean ± s.e.m. (E–H, L) Unpaired Student's t-test. (J, K) Two-way ANOVA. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Source data are available online for this figure.

Fig 5: Inhibition of sEH restored HG -induced impaired autophagy flux and mitophagy.a Western blot analysis of sEH in HK-2 cells treated with HG or/and t-AUCB for 24 h. b Densitometric analysis of sEH (n = 3, *P < 0.05 vs. LG, #P < 0.05 vs. t-AUCB). c ELISA kit analysis of sEH enzymatic activity (14,15-EET to 14,15-DHET ratios) in HK-2 cells (n = 3, *P < 0.05 vs. LG, #P < 0.05 vs. t-AUCB, ?P < 0.05 vs. HG). d Western blot analysis of Lamp2, Atg5, LC3-II/LC3-I, p62, PINK1 and Parkin in HK-2 cells treated with HG or/and t-AUCB for 24 h. e Representative images of MDC staining in different groups of HK-2 cells after treated with HG or/and t-AUCB for 24 h. f–k Densitometric analysis of Lamp2, Atg5,LC3-II/LC3-I, p62, PINK1 and Parkin in figure d (n = 3, *P < 0.05 vs. LG, #P < 0.05 vs. t-AUCB, ?P < 0.05 vs. HG). l Representative images of immunofluorescence double labeling of LC3 and P62 in different groups of HK-2 cells after treated with HG or/and t-AUCB for 24 h. m–o Colocalization analysis of immunofluorescence images of GFP-LC3 (green) and Lamp2 (red), GFP-LC3 (green) and Mito Tracker (red), GFP-LC3 (green) and Parkin (red) in different groups of HK-2 cells after treated with HG or/and t-AUCB for 24 h.