Feedback regulation of bile acid synthesis in the rat by dietary vs. Intravenous cholate or taurocholate



The regulation of bile acid synthesis was studied (i) in intact or colectomized rats receiving cholate or taurocholate as a dietary supplement and (ii) in experiments using chow-fed animals with a graded intravenous or intraduodenal taurocholate infusion. After the 2-week diet period a bile fistula was established and rates of taurocholate, tauromuricholate and taurochenodeoxy-cholate secretion were quantitated by high-performance liquid chromatography. During the infusion experiments taurocholate production was calculated from the difference in specific activity of [14C]taurocholate between infusate and bile, whereas tauromuricholate and taurochenodeoxycholate synthesis was derived directly from their secretion rates after pool depletion. Both the 0.5% cholate and taurocholate diet suppressed tauromuricholate and taurochenodeoxycholate secretion nearly totally, but only cholate led to a prolonged inhibition taurocholate synthesis. The diets stimulated total bile acid secretion and expanded the total bile acid pool size 2- to 3-fold, but they also prompted a dramatic increase in the biliary secretion of taurodeoxycholate. In contrast, colectomized animals did not secrete taurodeoxycholate following the cholate diet and, despite a comparable increase in bile acid pool size, tauromuricholate and taurochenodeoxycholate secretion was inhibited to a lesser extent. In addition, the rate of bile acid secretion and synthesis was significantly enhanced when compared to that of intact rats. To determine whether taurocholate affected bile acid synthesis directly, the bile acid was infused intravenously or intraduodenally at varying rates up to 300 μmoles per kg per hr for 54 hr, i.e. a rate exceeding normal total bile acid secretion in these acute bile fistula animals nearly 3-fold. However, there was no decrease in both tauromuricholate, and taurocholate synthesis and taurochenodeoxycholate was lowered only by the highest dose of taurocholate and only during the derepressed phase. When a taurocholate infusion was given to rats prefed 0.5% cholate there was no evidence for an enhanced feedback regulation by a preceding pool expansion. It is suggested that the suppressive effect of dietary cholate or taurocholate or bile acid formation may not be mediated by the primary bile acid directly, but rather by secondary bile acids formed in the colon.