Gender Differences in Bile Acid Kinetics After Dietary Challenges

Abstract

Apart from their role in lipid digestion and sterol homeostasis, bile acids (BA) are known to affect metabolism via FXR and TGR5 receptors. They also modulate energy expenditure and thus became a target in obesity research. As part of the Nutritech project, we analyzed the plasma kinetics of BA after dietary challenges. Healthy volunteers in fasting state underwent an oral glucose tolerance test (OGTT) with 75 g of glucose and blood withdrawals at 0, 15, 30, 60, 90, 120 and 240 minutes. In the following day, the same volunteers endured a mixed meal test (MMT) receiving a liquid meal and having blood samples collected at 0, 30, 60, 120, 240 and 360 minutes. Bile acids were analyzed in plasma by a LC‐MS/MS based method with stable‐isotope labeled reference standards. Both dietary challenges increased the plasma concentration of BA (around 3.85‐fold after the MMT and around 2‐fold after the OGTT). The increase of glycine‐conjugated BA was twice more pronounced than that of taurine‐conjugated entities, while naive BA showed no post‐prandial increase. The increase of primary BA was in average 25% more pronounced than that of secondary BA in both tests. Rather surprising was the finding of gender differences in the kinetics of BA after the OGTT which were not observed after the MMT. These differences originate from an earlier peak in plasma BA in men (at t=30 minutes), whereas women reached 30% higher levels of BA 60 minutes after the glucose ingestion. The observed differences between men and women may have different effects in view of metabolic regulation and their impact shall be considered in future studies.