Fig. 2: Acod1 ablation opposes liver steatosis and associated urea cycle dysfunction induced by dietary lipid overload. | Cell Death & Disease

Fig. 2: Acod1 ablation opposes liver steatosis and associated urea cycle dysfunction induced by dietary lipid overload.

From: ACOD1 deficiency offers protection in a mouse model of diet-induced obesity by maintaining a healthy gut microbiota

Fig. 2

A Weights of livers from WT and Acod1-/- mice fed with ND (n = 4) or HFD (n = 8) for 16 weeks. Data as mean±s.e.m. from one experiment out of three independently executed. B Representative H&E staining of livers from mice described in A, Bar = 100 μm. C Liver triglycerides in mice described in A; ND (n = 6), HFD-WT (n = 10), HFD-Acod1-/- (n = 8). Data as mean±s.e.m. from two independent experiments. Venn diagram (D) and KEGG-based functional enrichment analysis (E) of upregulated proteins in livers of WT mice fed with HFD compared with ND-fed mice (HFD vs ND [WT]) and rescued by Acod1 loss (Acod1-/- vs WT [HFD]). Data derive from n = 5 ND-fed (WT), n = 8 (ND-fed Acod1-/-) and n = 6 (HFD-fed) mice from two independent experiments. (F) Heatmap of protein levels described in D. G Pearson’s correlation between changes in liver free fatty acid (FFA) levels in HFD-fed WT mice (HFD vs ND [WT]) and by Acod1 loss (Acod1-/- vs WT [HFD]); n = 6 pre group. Data from two independent experiments. H Heatmap depicting diacylglycerol levels in livers of mice treated as in A. Data derive from n = 5 (ND-fed), n = 5 (HFD-fed WT), n = 6 (HFD-fed Acod1-/-) mice from one experiment. I Venn diagram (left) and gene ontology (biological processes)-based functional enrichment analysis (right) of downregulated proteins in livers of WT mice fed with HFD compared with ND-fed mice (HFD vs ND [WT]) and rescued by Acod1 loss (Acod1-/- vs WT [HFD]). J Heatmap of protein levels described in I. K Levels of the indicated urea cycle metabolites in liver of mice fed with either ND or HFD for 16 weeks. Data derive from n = 5 (ND-fed wild type), n = 8 (ND-fed Acod1-/-), n = 6 (HFD-fed wild type), and n = 7 (HFD-fed Acod1-/-) mice from two independent experiments; Arg.succ argininosuccinate, NAG N-Acetylglutamate. L Levels of NH3 in liver of mice fed with either ND or HFD for 16 weeks. Data derive from n = 6 (ND), n = 7 (HFD)-fed mice from two independent experiments. In K and L, boxes extend from 25th to 75th percentiles, black lines=median, whiskers=minimum to maximum. In (A) one-way ANOVA with Dunnett’s multiple comparisons test compared to HFD-fed WT mice; In C, (K, L): t-test. *P < 0.05; **P < 0.01; ***P < 0.001; ns not significant.

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