Caloric Restriction and Dietary Taurine Regulate Taurine Homeostasis Through Distinct Tissue‐Specific Mechanisms in Mice

Caloric restriction (CR) stimulates taurine-conjugated bile acids (BA) synthesis in the liver. Upon secretion into the intestine, BAs undergo deconjugation, increasing taurine, and taurine conjugate levels, including taurine-glutathione (GSH). This study aimed to determine whether dietary taurine and CR-induced taurine changes operate through distinct regulatory mechanisms. Male C57Bl/6 mice were subjected to ad libitum feeding or 20% CR with low-taurine diet (LTD) or 5% taurine in drinking water. LTD and taurine supplementation minimally affected intestinal taurine concentrations and did not disrupt CR-induced changes in intestinal taurine levels, GSH conjugates, and GST expression, demonstrating mechanistic independence. Both interventions significantly altered hepatic and plasma taurine levels, indicating tissue-specific regulation. While CR primarily influenced GSH-S transferase (GST) mRNA expression in the intestine, GST activity correlated with substrate availability rather than gene expression. CR maintained enhanced intestinal taurine retention during taurine supplementation, evidenced by reduced fecal taurine excretion compared to controls. Dietary and CR-related taurine are affected by distinct tissue-specific mechanisms, with CR primarily impacting intestinal taurine while modulation of dietary taurine (restriction or supplementation) predominantly influences hepatic pools. The study reveals independent regulatory mechanisms governing taurine homeostasis and emphasizes differences between dietary factors and physiological responses during CR.