Intestinal cholesterol absorption and bile acid transport pathways

The intestinal cholesterol absorption and bile acid transport pathways represent a complex network of transporters responsible for the uptake of dietary lipids and the recycling of bile salts. The primary molecular targets within these pathways are the Niemann-Pick C1-Like 1 (NPC1L1) protein and the Apical Sodium-dependent Bile acid Transporter (ASBT, also known as SLC10A2) (Betters & Yu, 2010, Journal of Molecular Medicine). NPC1L1 is essential for the absorption of cholesterol from the intestinal lumen into enterocytes, while ASBT facilitates the reabsorption of approximately 95% of bile acids in the terminal ileum as part of the enterohepatic circulation (Dawson et al., 2009, Journal of Lipid Research). Disruptions or overactivity in these pathways are linked to hypercholesterolemia, atherosclerosis, and cholestatic liver diseases characterized by debilitating pruritus (Al-Dury & Marschall, 2018, Journal of Internal Medicine). Pharmacological intervention typically involves small molecule inhibitors: ezetimibe targets NPC1L1 to lower LDL cholesterol, whereas ASBT inhibitors like odevixibat and maralixibat are used to reduce the systemic bile acid pool and treat cholestatic symptoms (Gleeson et al., 2017, Current Opinion in Lipidology). These therapies are valued for their localized action within the gastrointestinal tract, though they can lead to side effects such as diarrhea and potential malabsorption of fat-soluble vitamins.

Other names

Intestinal lipid absorption pathwayEnterohepatic circulation of bile acidsNPC1L1-ASBT axisBile acid and cholesterol transport system

Inhibition of specific apical membrane transporters (NPC1L1 for cholesterol and ASBT for bile acids) to prevent intestinal absorption and promote fecal excretion of sterols and bile salts.