A FUNCTION FOR BILE ACIDS IN THE BRAIN
Supervisors: Maarten Soeters, Anita Boelen, Hans Romijn & Andries Kalsbeek
Bile acids (BAs) are nutrion-emulgators essential for lipid digestion and cholesterol metabolism. The primary BAs cholic acid (CA) and chenodeoxy cholic acid (CDCA) are synthesized in the liver from cholesterol. In the gut they are dehydroxylated to deoxycholic acid (DCA) and lithocholic acid (LCA), respectively. BAs are reabsorbed in the entero-hepatic circulation and transported back to the liver. However, recently it has become apparent that after re-uptake BAs may also function as signalling molecules and play a role in energy metabolism.
Bile acids function through the nuclear receptor FXR and the G-protein-coupled receptor TGR5. Through these receptors in different organs BAs influence lipid storage, insulin sensitivity and glucose metabolism. The FXR and TGR5 are also present in the brain; however studies of the function of central BAs have not yet been reported.
We hypothesize that central BA signalling modulates postprandial responses with direct effects on BA, lipid, glucose, and energy metabolism, but also food intake and satiety.
In a related project funded by the Dutch Diabetes Fonds we investigate whether bile acids regulate insulin sensitivity and postprandial glucose and lipid metabolism in healthy humans and patients with type 2 diabetes mellitus.
In my project we study the possible effects of BA on the central nervous system. In the first experiment we investigate the role of bile acids in the brain by intracerebroventricular administration of bile acids in vivo and analysing its effects using different techniques such as real time PCR and c-fos immunocytochemistry.
Overview of the (possible) roles of bile acids through the FXR and TGR5 receptor in different organs.