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Lithocholic acid (LCA) feeding resulted in severe liver damage and activation of the NLRP3 inflammasome
Kupffer cells (KC) were the most affected cells, resulting in a pro-inflammatory phenotype .
Lithocholic acid (LCA) is the main bile acid ligand for the pregnane X receptor, Vitamin D receptor (VDR) is activated by LCA, but not by other Bile acids / Bile salts
LCA suppresses activation of NLRP3 inflammasome via theTGR5 signaling in DCs and macrophages, while CDCA inhibits production of NFKB -dependent expression of inflammatory mediators in a FXR-dependent fashion
Lithocholic Acid and Deoxycholic Acid Are Normally the Most Abundant Gut Secondary Bile Acids
Lithocholic acid is the most hydrophobic bile acid
Only a small amount of LCA is reabsorbed into the enterohepatic circulation
As a result, the LCA level in the feces is higher
LCA is hepatotoxic and undergoes sulfation at the C3 position, a modification that prevents intestinal reabsorption and promotes its elimination via feces
Second step: dehydroxylation at the C7α position to generate the secondary bile acids deoxycholic acid (DCA) or lithocholic acid (LCA), respectively (predominantely in Clostridium sp.)
Secondary bile salts (LCA>DCA) display higher affinity for TGR5 than primary (CDCA>CA) bile salts
The order of potency for binding to FXR of endogenous bile salts is CDCA>DCA=LCA>CA
Lithocholic acid controls adaptive immune responses by inhibition of Th1 activation through the Vitamin D receptor (VDR)
Secondary Bile Acids, Deoxycholic and Lithocholic Acids, Are also Putative Tumor Promoters (cocarcinogenic)