Inhibition of Cholesterol Absorption

Living reference work entry

Abstract

Acyl coenzyme A:cholesterol acyltransferase (ACAT), which catalyzes the intracellular formation of cholesteryl esters, plays an important role in the intestinal absorption of cholesterol, foam cell formation within the arterial wall, and VLDL production in the liver. Two isoforms of the enzyme exist, ACAT1 expressed in macrophages and ACAT2 expressed in intestine and liver. Cholesterol is absorbed from the gut exclusively in the unesterified form but appears in the lymph esterified with various long-chain unsaturated fatty acids. The enzyme responsible is ACAT, a microsomal enzyme that utilizes long-chain fatty acyl coenzyme A and cholesterol as substrates. ACAT inhibitors also have potential actions beyond inhibition of cholesterol absorption. Inhibition of hepatic ACAT could reduce the production of cholesteryl esters for packaging into lipoproteins, while inhibition of ACAT1 in macrophages could reduce the deposition of cholesteryl esters and prevent the formation of foam cells and atherosclerotic lesions (Nissen et al. 2006; Pal et al. 2013; Rudel and Farese 2006). Nevertheless, from investigations in ACAT2 knockout mice, it is known that ACAT2 is not the only rate-limiting pathway for cholesterol absorption. On normal chow, these mice absorb cholesterol as efficiently as wild-type mice, only if mice were fed a cholesterol-enriched diet. ACAT2 is important for cholesterol absorption (Lee et al. 2004; Repa et al. 2004). Under physiological conditions, alternative pathways compensate for the ACAT2 deficiency in mice (Hussain et al. 2005).

Keywords

Cholesterol Absorption Cholesteryl Ester Cholesterol Acyltransferase ACAT2 Deficiency Acyl Coenzyme 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Further Reading

Inhibition of ACAT (Acyl Coenzyme A: Cholesterol Acyltransferase): General Considerations

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Lymph Fistula Model for Cholesterol Absorption

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Physiology, UMR CNRS 7213Université de StrasbourgIllkirchFrance
  2. 2.Johann Wolfgang Goethe-Universität Frankfurt am MainFrankfurt am MainGermany

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