Cholesterol and bile acid metabolism

Dietary cholesterol and bile acids are integral components of the body's lipid metabolism and enterohepatic circulation (Patti et al., 2005, Journal of Biological Chemistry). Dietary cholesterol is primarily absorbed in the proximal small intestine via the Niemann-Pick C1-Like 1 (NPC1L1) protein, contributing to systemic cholesterol levels (Altmann et al., 2004, Science). Bile acids, synthesized from cholesterol in the liver, are secreted into the duodenum to emulsify fats and facilitate the absorption of dietary lipids and fat-soluble vitamins (StatPearls, 2023, "Bile Acid Sequestrants"). Beyond digestion, bile acids act as potent signaling molecules that activate the Farnesoid X Receptor (FXR) and the G protein-coupled bile acid receptor (TGR5), which regulate glucose, lipid, and energy homeostasis (Thomas et al., 2008, Nature Reviews Drug Discovery). Dysregulation of these pathways is a major driver of cardiovascular diseases like atherosclerosis and metabolic liver diseases such as non-alcoholic steatohepatitis (NASH) (Patti et al., 2005, Journal of Biological Chemistry). Therapeutic strategies include inhibiting cholesterol absorption with drugs like ezetimibe, using bile acid sequestrants to lower LDL cholesterol, and employing FXR agonists to treat cholestatic liver diseases (StatPearls, 2023, "Bile Acid Sequestrants").

Other names

Dietary cholesterol and bile acidsEnterohepatic circulationBile acid signalingCholesterol absorption pathway

Inhibition of intestinal cholesterol absorption via NPC1L1; sequestration of bile acids in the intestinal lumen to prevent enterohepatic recirculation; activation of the Farnesoid X Receptor (FXR) to modulate bile acid synthesis and transport.