Figure 5.

Role of Akr1b7 in bile acids metabolism and signaling pathway. Akr1b7 has the ability to reduce 3-keto bile acids to their less toxic 3β-hydroxy derivatives. In turn, bile acids can stimulate detoxification activity of Akr1b7, enhancing its capacity to reduce carbonyl and 3-keto bile acids. In addition to bile acids detoxification, Akr1b7 is also one of their target genes. In liver and intestine, bile acids induce the FXR-dependent Akr1b7 transcription. The forced expression of Akr1b7 in mouse liver by the mean of recombinant adenovirus results in the down-regulation of gluconeogenesis and lipid metabolism. Mechanisms involved are not unravel yet but could rely on the up-regulation of SHP expression. Increased SHP levels could in turn repress both FOXO and LXR, leading to the inhibition of gluconeogenic genes and lipogenic genes, respectively. The mechanism by which Akr1b7 accumulation modulates the SHP gene expression appears independent from FXR and remains to be discovered (dashed lines).