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Articles

Molecular Mechanisms of Sterol Absorption¹

Gladstone Institute of Cardiovascular Disease, Division of Endocrinology and Department of Medicine, University of California, San Francisco, CA 94141

Recent studies have significantly advanced our understanding of intestinal sterol absorption at the molecular level. Nuclear hormone receptors (such as liver X receptor, farnesoid X receptor and retinoid X receptor) regulate the absorption of dietary sterols by modulating the transcription of several important genes involved in cholesterol metabolism. One of these genes encodes a molecule [adenosine triphosphate-binding cassette (ABC) transporter] that transports dietary cholesterol from enterocytes back out to the intestinal lumen, thereby limiting the amount of cholesterol absorbed. ABC transporters also provide an efficient barrier against the absorption of plant sterols. Another key process that affects intestinal sterol absorption is the synthesis of cholesterol esters. Mice lacking the enzyme for cholesterol esterification in the small intestine have a reduced capacity to absorb dietary cholesterol and are protected against diet-induced hypercholesterolemia and gallstone formation. In addition to elucidating some of the molecular mechanisms of sterol absorption, these recent findings may lead to new therapeutic options to treat hypercholesterolemia.

KEY WORDS: • sterols • intestinal absorption • nuclear hormone receptors • ABC transporters • sitosterolemia • cholesterol esters

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