Popping the soap bubble: Bile acids as postrandial signal

Bile acids are not merely soaps to aid lipid absorption but also function as signaling molecules in glucose, lipid, and their own metabolism. Bile acids are synthesized in the liver, stored in the gallbladder and released into the small intestines after food intake. Most of the bile acids are reabsorbed from the intestines and travel back to the liver. This is called the enterohepatic circulation. A small percentage of the total bile acid pool escapes hepatic clearance and, therefore, bile acids are also present in the systemic circulation. After food intake (“postprandial”) the concentration of bile acid rises. There are various receptors that can bind bile acids, the ones involved in energy metabolism and described in this thesis are the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). FXR and TGR5 are highly expressed within the enterohepatic circulation, but also outside, for example in adipose tissue and the brain. Therefore, the notion emerged that circulating bile acids might serve as postprandial messengers through these receptors. We aimed to investigate whether the metabolic effects of bile acids were exerted via the brain. For this purpose, we studied several aspects of bile acid metabolism with regard to postprandial hepatic kinetics, day-night rhythm, food paradigms and effects in the brain