Glutathione Contributes to Caloric Restriction-Triggered Shift in Taurine Homeostasis

Area of Science:

• Metabolic regulation
• Nutrient absorption
• Bile acid metabolism

Background:

• Caloric restriction (CR) increases intestinal taurine levels via bile acid deconjugation.
• Taurine conjugates with glutathione (GSH) in the intestine.
• Understanding the mechanisms and consequences of taurine-GSH formation in CR is crucial.

Purpose of the Study:

• Investigate the mechanisms of taurine-GSH conjugate formation.
• Determine the impact of taurine-GSH on taurine, other taurine conjugates, and bile acids (BA) under CR.
• Elucidate the role of this network in CR-induced metabolic adaptations.

Main Methods:

• Assessed non-enzymatic conjugation of taurine and GSH.
• Verified uptake of taurine, GSH, and taurine-GSH in intestinal segments.
• Measured taurine, labeled taurine, taurine conjugates, taurine-GSH, and GSH in ad libitum and CR mice.
• Inhibited taurine transporter (SLC6A6) and GSH-S transferases (GST) to challenge the CR phenotype.

Main Results:

• CR increased intestinal taurine, with subsequent organ distribution.
• Tissues exhibited unique taurine conjugate profiles.
• While non-enzymatic formation occurred, GST activity was key to CR outcomes.
• Inhibiting SLC6A6 and GST primarily affected the ileum, impacting BA levels differently in the ileum and liver.

Conclusions:

• CR establishes a regulatory network for taurine and bile acid homeostasis.
• Glutathione conjugation of taurine is vital for this network.
• This conjugation influences intestinal taurine uptake and the availability for other conjugates.