Additional file 2 of The essential roles of FXR in diet and age influenced metabolic changes and liver disease development: a multi-omics study
Creators: name: Yang, Guiyan
name: Jena, Prasant K.
name: Hu, Ying
name: Sheng, Lili
name: Chen, Shin-Yu
name: Slupsky, Carolyn M.
name: Davis, Ryan
name: Tepper, Clifford G.
name: Wan, Yu-Jui Yvonne
Publisher: name: figshare
Year: 2023
Subjects: subject: Biochemistry
subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Physiology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Cancer
subject: Computational Biology

description: Additional file 2: Fig. S2. Heatmaps show the fold changes of WD-altered 36 transcripts in (A) WT mice and 6 transcripts in (B) FXR KO mice regardless of ages (fold change ≥2 and adjusted p value &lt; 0.05). Fig. S3. Altered liver metabolites due to differential dietary intake. (A) Diet altered metabolites in both WT and FXR KO mice. (B) Diet changed metabolites only in WT or FXR KO mice (raw p value &lt; 0.05 and FDR &lt; 0.1). Fig. S4. The effects of diets on hepatic bile acids in WT and FXR KO mice. (A) Principal component analyses of hepatic bile acids of WT and FXR KO mice fed with either a CD or WD. (B) Venn diagrams show the numbers of distinct and overlapping bile acids that were changed by differential diets intake in 3 age groups (p &lt; 0.05). (C) A heatmap of relative concentrations of hepatic bile acids. Fig. S5. The effects of diets on serum metabolomes in WT and FXR KO mice. (A) Principal component analyses of serum metabolomes of WT and FXR KO mice fed with either a CD or WD. (B) Venn diagrams show the numbers of distinct and overlapping metabolites that were changed by differential diets intake in 3 age groups (raw p value &lt; 0.05 and FDR &lt; 0.1). The metabolites in purple were affected by diet in both genotypes. Fig. S6. The effects of diets on urine metabolomes in WT and FXR KO mice. (A) Principal component analyses of urine metabolomes of WT and FXR KO mice. (B) Venn diagrams show the numbers of distinct and overlapping metabolites that were changed due to differential diet intake in 3 age groups (raw p value &lt; 0.05 and FDR &lt; 0.1). The metabolites in purple are commonly affected by diet in both genotypes. Fig. S7. The effects of diets on cecal microbiota. (A) Principal component analyses of cecal microbiota at genus level of WT and FXR KO mice fed with either a CD or WD. (B) Venn diagrams show the numbers of distinct and overlapping cecal microbiota at the genus level that were changed by differential diets intake in 3 age groups (raw p value &lt; 0.05). Fig. S8. Age altered liver metabolites in WT and FXR KO mice. (A) Heatmap of metabolites that changed due to age (15 vs. 5) shared in both WT and FXR KO mice. (B) Age-changed metabolites in WT or FXR KO mice (raw p value &lt; 0.05 and FDR &lt; 0.1). Fig. S9. The influence of ages on hepatic bile acids in WT and FXR KO mice. (A) Principal component analyses of hepatic bile acids of 5- or 15-month-old WT and FXR KO mice fed with either a CD or WD. (B) Venn diagrams show the numbers of distinct and overlapping bile acids that were changed in two age groups. Fig. S10. The influence of ages on serum metabolomes in WT and FXR KO mice. (A) Principal component analyses of serum metabolomes of 5- or 15-month-old WT and FXR KO mice fed with either a CD or WD. (B) Venn diagrams show the numbers of distinct and overlapping metabolites that were changed in two age groups. The metabolites in purple were commonly affected by ages in both genotypes (raw p value &lt; 0.05 and FDR &lt; 0.1). Fig. S11. The influence of ages on urine metabolomes in WT and FXR KO mice. (A) Principal component analyses of urine metabolomes of 5- or 15-month-old WT and FXR KO mice fed with either a CD or WD. (B) Venn diagrams show the numbers of distinct and overlapping metabolites that were changed by age (raw p value &lt; 0.05 and FDR &lt; 0.1). The metabolites in purple are commonly affected by age in both genotypes. Fig. S12. The influence of ages on cecal microbiota in WT and FXR KO mice. (A) Principal component analyses of cecal microbiota at genus level of 5- or 15-month-old WT and FXR KO mice fed with either a CD or WD . (B) Venn diagrams show the numbers of distinct and overlapping bacteria at the genus level that were changed by age (raw p value &lt; 0.05). Fig. S13. Altered liver metabolites due to FXR KO. (A) A heatmap shows FXR KO-altered metabolites commonly found in mice with either a CD or WD. (B) FXR KO changed metabolites in WT or FXR KO mice (raw p value &lt; 0.05 and FDR &lt; 0.1). Fig. S14. The effects of FXR KO on hepatic bile acids. (A) Principal component analyses of serum metabolomes of WT and FXR KO mice fed with either a CD or WD and euthanized when they were 5, 10, and 15 months old. (B) Venn diagrams show the numbers of distinct and overlapping metabolites that were altered by FXR KO in CD- and WD-fed mice (raw p value &lt; 0.05 and FDR &lt; 0.1). Fig. S15. The effects of FXR KO on serum metabolomes. (A) Principal component analyses of serum metabolomes of WT and FXR KO mice fed with either a CD or WD and euthanized when they were 5, 10, and 15 months old. (B) Venn diagrams show the numbers of distinct and overlapping metabolites that were altered by FXR KO in CD- and WD-fed mice (raw p value &lt; 0.05 and FDR &lt; 0.1). The metabolites in purple were commonly changed by FXR KO in both CD- and WD-fed mice. Fig. S16. A heatmap shows serum metabolite levels in WT and FXR KO mice fed with either a CD or WD for different durations. Fig. S17. The effects of FXR KO on urine metabolomes. (A) Principal component analyses of urine metabolomes of WT and FXR KO mice fed with either a CD or WD and euthanized when mice were 5, 10, and 15 months old. (B) Venn diagrams show the numbers of distinct and overlapping metabolites that were altered by FXR KO in CD- and WD-fed mice (raw p value &lt; 0.05 and FDR &lt; 0.1). The metabolites in purple were commonly changed by FXR KO in both CD- and WD-fed mice. Fig. S18. A heatmap shows urine metabolite levels in WT and FXR KO mice fed with either a CD or WD for different durations. Fig. S19. The effects of FXR KO on cecal microbiota. (A) Principal component analyses of cecal microbiota at genus level of WT and FXR KO mice fed with either a CD or WD and euthanized when mice were 5, 10, and 15 months old. (B) Venn diagrams show the numbers of distinct and overlapping bacteria that were altered by FXR KO in CD- and WD-fed mice. The bacteria in purple were commonly changed by FXR KO in both CD- and WD-fed mice. (C) A heatmap of relative abundances of cecal microbiota at genus level that were changed by FXR KO irrespective of ages (raw p value &lt; 0.05). Fig. S20. Common changes in hepatic metabolites due to WD intake, aging, and FXR KO. Venn diagram shows the number of altered metabolites by each risk factor. Heatmap of 44 hepatic metabolites that were commonly altered by diet, age, and FXR KO (raw p value &lt; 0.05 and FDR &lt; 0.1). Fig. S21. Spearman’s correlation analysis between hepatic features (76 transcripts and 44 metabolites that were commonly altered by diet, age, and FXR KO) and serum/urine metabolites as well as cecal microbiota at the genus level. *p &lt; 0.05, **p &lt; 0.01 with Hochberg correction. Upregulated transcripts are in red, while downregulated ones are in blue. Fig. S22. Diet, age, and FXR KO altered hepatic, serum, and urine metabolites involved in the urea cycle, TCA cycle, and methionine cycle.