[4] There are also species differences in the G/T ratio, with this ratio being lower in rodents than in humans. This may be due to the higher rate of taurine biosynthesis in rodents. However, the G/T ratio does not

seem to influence the total output of bile acids from the liver or fat absorption in the intestine. Thus, it is unclear if one purpose of FXR activation is to induce an increase in the G/T ratio through repression of taurine drug discovery biosynthesis in mice. Beneficial effects of taurine on liver diseases have been established in many previous studies, including those from our laboratory.[5-8] Both intestinal absorbance of taurine from an exogenous source and cellular taurine uptake are carried out through a specific taurine transporter (TAUT). Cilomilast molecular weight A study in a TAUT-knockout mouse showed that maintenance of the taurine pool in vivo is important to prevent liver damage and that the hepatic taurine pool in mice depends mainly on exogenous uptake, rather than on endogenous biosynthesis.[9] Inhibition of taurine biosynthesis induced by FXR activation would further increase the need for oral taurine intake. Many studies in experimental animal models have shown the efficacy

of taurine treatment for hypercholesterolemia induced exogenously by a high cholesterol diet and endogenously by diabetes and some xenobiotics, through a mechanism of increased cholesterol catabolism to bile acids and bile acid excretion to bile.[10] In these studies, taurine feeding resulted in

significantly enhanced fecal bile acid excretion and increased CYP7A1 activity and mRNA expression. The mechanism of CYP7A1 regulation by taurine is unclear, but taurine may influence activation of liver X receptor-α (LXRα), a promoter of CYP7A1 transcription.[11] However, a binding site for LXRα on the cyp7a1 gene is present in mice but not in humans, indicating that there also may be a species difference in taurine regulation of cholesterol metabolism between humans and mice. Clinical trials of synthetic FXR ligands (e.g. GW4064, INT747) for lipid PIK3C2G metabolism-related diseases are in progress. Kerr et al. show that FXR activation can regulate taurine biosynthesis, in addition to bile acid metabolism, in mice. Because taurine has many physiological effects, including bile acid conjugation, in many species, it is clearly important to consider the taurine pool and function when using synthetic FXR ligands as drugs. The apparent species differences in regulation of lipid metabolism and the balance of bile acid conjugation emphasize the importance of careful examination of these mechanisms in humans. “
“The 14th Taishotoyama International Symposium on Gastroenerology was planned for 2 days from 15 to 16 April last year. However, the Symposium was canceled due to the unprecedented disaster. The scenes of this disaster are still fresh in our memory. The massive 9.