*3.2. Liver Damage in Response to LCA Feeding is Aggravated in TGR5 KO Mice and Results in Increased Portal Pressure*

Liver damage in response to LCA feeding was more pronounced in TGR5 KO mice as compared to WT mice, as demonstrated by significantly higher serum levels of AST (WT LCA (*n* = 12) 6586 ± 898 IU/L vs. KO LCA (*n* = 10) 10,629 ± 1422 IU/L (1.6-fold increase), *p* < 0.05) and more extensive bile infarcts on liver histology (Figure 2A–C). Furthermore, a significant increase in portal venous pressure was observed in LCA-fed TGR5 KO mice as compared to LCA-fed WT or chow-fed TGR5 KO mice, respectively (WT LCA (*n* = 7) 3.9 ± 0.4 cmH20 vs. KO LCA (*n* = 6) 5.7 ± 0.6 cmH20 (1.4-fold increase), *p* < 0.05) (Figure 2D). There was no difference in portal pressure between chow-fed mice of both genotypes.

**Figure 2.** LCA feeding induces a more pronounced liver injury in TGR5 knockout mice as compared to littermate controls. (**A**) Hematoxylin and eosin staining of representative liver sections from wildtype mice fed with either a chow or LCA-enriched diet (1% *wt*/*wt*) for 84 h. (**B**) H&E staining of liver sections from TGR5 knockout (KO) mice. LCA feeding results in a more severe liver injury in TGR5 KO mice as compared to controls. Bars = 50 μm. (**C**) Serum AST and ALT-levels (in IU/l) increase significantly in mice of both genotypes following LCA feeding (*n* = 10–12 for LCA-fed and *n* = 4 for chow-fed mice of each genotype). (**D**) Measurement of portal vein perfusion pressure (in cm H20) of wildtype (WT) and TGR5 KO mice fed with either chow or LCA diet (*n* = 5–7). All data are shown as mean ± standard error of the mean (SEM). \* Statistically significant difference between the LCA- and chow-fed mice of the same genotype (*p* < 0.05); # statistically significant difference between WT and TGR5 KO mice fed the same diet (*p* < 0.05).
