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About Bile Acids and IBAT Inhibition

The liver is responsible for many vital body functions, including the regulation of bile acid synthesis and metabolism. The liver uses cholesterol to produce bile acids. Once produced, bile acids are transported and stored in the gall bladder. In response to food ingestion, the gall bladder contracts and releases bile acids into the small intestine where they promote digestion and absorption of dietary fats and fat­soluble vitamins A, D, E and K. After completing digestion, bile acids are reclaimed in the distal part of the small intestine, known as the terminal ileum, by the ileal bile acid transporter (IBAT). As depicted below, the IBAT initiates the transport of bile acids, which flow through the portal vein back to the liver in a process known as enterohepatic circulation.

liver

In enterohepatic circulation, approximately 95% of bile acids recirculate back to the liver, with the remaining 5% being secreted to the colon. The liver must produce a small amount of new bile acids every day to make up for this loss.

In addition to their role in digestion, bile acids are important signaling molecules that help regulate a network of metabolic pathways throughout the GI system. Bile acids bind to receptors in the colon that promote the release of intestinal hormones, such as glucagon­like peptide­1 (GLP­1), that can stimulate insulin release from the pancreas and over time decrease levels of plasma hemoglobin A1c (HbA1c), a measure of glucose, or blood sugar. In the liver, bile acids bind to other receptors that regulate bile acid production from cholesterol in a negative feedback loop. Under normal conditions, bile acids bind to these receptors and inhibit the synthesis of new bile acids. As bile acid levels are lowered, the liver must produce needed bile acids from cholesterol, which requires increased uptake of cholesterol and a resulting decrease of cholesterol in the liver.

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