bile acid signaling pathway

Definition

Target type: biologicalprocess

The series of molecular signals initiated by bile acid binding to its receptor, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:bf, GOC:signaling, PMID:12016314]

Bile acid signaling is a complex and multifaceted process that involves a series of events beginning with the synthesis of bile acids in the liver, their release into the bile, and their subsequent journey through the digestive tract. This process plays a critical role in lipid digestion and absorption, but also extends to a broad range of physiological functions beyond the gut, including metabolic regulation, energy expenditure, inflammation, and even the modulation of the gut microbiota. Here's a breakdown of the key steps involved:

**1. Bile Acid Synthesis:**

* Bile acids are synthesized from cholesterol in the liver, primarily through the classical and alternative pathways.
* The classical pathway, involving the cytochrome P450 enzymes CYP7A1 and CYP8B1, is the main route for bile acid synthesis.
* The alternative pathway, which utilizes CYP27A1, is less active but becomes crucial when the classical pathway is impaired.
* The primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), are synthesized in the liver and conjugated with glycine or taurine to form bile salts, which are more water-soluble and thus easier to excrete.

**2. Bile Secretion:**

* Bile salts, along with other bile components like phospholipids and cholesterol, are secreted into the bile canaliculi, small channels that drain into the bile ducts.
* The bile ducts transport the bile to the gallbladder, where it is concentrated and stored.

**3. Bile Release:**

* When food enters the duodenum, the hormone cholecystokinin (CCK) is released, stimulating the gallbladder to contract and release bile into the small intestine.

**4. Bile Acid Digestion and Absorption:**

* Bile acids facilitate the digestion and absorption of lipids in the small intestine by acting as detergents, emulsifying fat globules into smaller droplets.
* This increases the surface area for lipase enzymes to break down fats into fatty acids and monoglycerides, which can then be absorbed by the intestinal lining.

**5. Enterohepatic Circulation:**

* Only a small fraction of bile acids is excreted in the feces.
* The majority are reabsorbed in the terminal ileum and return to the liver through the portal vein, a process known as enterohepatic circulation.
* This recycling ensures efficient utilization of bile acids and maintains their concentration in the body.

**6. Bile Acid Signaling:**

* Bile acids activate nuclear receptors like the farnesoid X receptor (FXR) and the vitamin D receptor (VDR), as well as G protein-coupled receptors (GPCRs) like TGR5, in various tissues, including the liver, intestine, and adipose tissue.
* Activation of these receptors triggers signaling cascades that regulate gene expression and cellular functions.

**7. Effects of Bile Acid Signaling:**

* **Metabolic Regulation:** Bile acids play a crucial role in regulating lipid metabolism, glucose homeostasis, and energy expenditure. They suppress hepatic glucose production, enhance insulin sensitivity, and promote fatty acid oxidation.
* **Gastrointestinal Function:** Bile acids contribute to proper digestion and absorption of fats, maintain gut motility, and influence the composition of the gut microbiota.
* **Inflammation:** Bile acids have been shown to modulate inflammatory responses, both promoting and inhibiting inflammation depending on the context.
* **Beyond the Gut:** Bile acids are also involved in regulating immune responses, influencing neurotransmission, and even affecting cardiovascular health.

**8. Dysregulation of Bile Acid Signaling:**

* Alterations in bile acid metabolism and signaling can contribute to a variety of diseases, including liver diseases, metabolic disorders like obesity and type 2 diabetes, inflammatory bowel disease, and even certain types of cancer.

Overall, bile acid signaling represents a complex and highly regulated system with diverse physiological functions, making it an important target for the development of novel therapies for a wide range of diseases.
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Proteins (5)

Compounds (1,242)