Fig. 4: Acod1 loss decreases diet-induced obesity-associated meta-inflammation.

A Venn diagram (left) and gene ontology (biological processes)-based functional enrichment analysis (right) of upregulated genes in eWAT of WT mice fed with HFD for 16 weeks compared with ND-fed mice (HFD vs ND [WT]) and rescued by Acod1 loss (Acod1^-/- vs WT [HFD]). Data derive from n = 4 (ND-fed WT) and n = 5 (HFD-fed) mice from one experiment. B Heatmap depicting the mRNA levels of selected genes defining macrophage markers, inflammatory cytokines and receptors, regulators of innate immunity, TLR signaling and TNF signaling upregulated in response to HFD (HFD vs ND [WT], FDR < 0.1) and rescued by Acod1 loss (Acod1^-/- vs WT [HFD], FDR < 0.1) in eWAT. Data derive from mice described in A: n = 4 (ND-fed WT) and n = 5 (HFD-fed) mice from one experiment. C Representative images (left) of immunohistochemistry staining for the macrophage marker F4/80 (Adgre1) in eWAT of WT and Acod1^-/- mice after 16 weeks on HFD diet. Red arrows indicate crown-like structures. D Quantification of the F4/80-positive area per field of view (FOV) in images described in C. (n = 5 mice per group, average of 5 images each). Red arrows indicate crown-like structures. Bars, 100 μm. Data are represented as mean ± s.e.m. *P < 0.05 (t-test). E qPCR analysis of Il1b mRNA levels in BAT of WT and Acod1^-/- mice after 16 weeks on HFD diet. Data as as mean±s.e.m of n = 11 (WT) and n =n = 8 (Acod1^-/-) mice from two independent experiments. *P < 0.05 (t-test). F Levels of the indicated pro-inflammatory cytokines in plasma of WT and Acod1^-/- mice after 16 weeks on HFD diet. Data as as mean±s.e.m of n = 8 (WT) and n = 9 (Acod1^-/-) mice from two independent experiments. *P < 0.05 (t-test).