Abstract
Cholesterol is an essential molecule that exerts pleiotropic actions. Although its presence is vital to the cell, its excess can be harmful and, therefore, sustaining cholesterol homeostasis is crucial to maintaining proper cellular functioning. It is well documented that high plasma cholesterol concentration increases the risk of atherosclerotic heart disease. In the last decades, several studies have investigated the association of plasma cholesterol concentrations and the risk of cardiovascular diseases as well as the signaling pathways involved in cholesterol homeostasis. Here, we present an overview of several mechanisms involved in intestinal cholesterol absorption, the regulation of cholesterol synthesis and uptake. We also discuss the importance of reverse cholesterol transport and transintestinal cholesterol transport to maintain cholesterol homeostasis and prevent atherosclerosis development. Additionally, we discuss the influence of dietary cholesterol on plasma cholesterol concentration and the new recommendations for cholesterol intake in a context of a healthy dietary pattern.
Highlights
Cholesterol is an important cellular molecule involved in the maintenance of membrane permeability and fluidity, and in the modulation of transmembrane signaling pathways, as well as in the synthesis of steroid hormones, bile acids and vitamin D [1,2,3]
The ubiquitination promoted by gp78 and Tcr8 allows the recognition of HMG-CoA reductase by an ATPase known as vasolin-containing protein (VCP or p97) that induces the proteasomal degradation of the reductase in a sterol-Insig dependent manner [34,36,37,38]
Library for the use of statins in primary prevention found reductions in all-cause mortality and major vascular events among people without evidence of cardiovascular disease (CVD) [46,47]. Another point of control on cholesterol synthesis occurs in a later step catalyzed by squalene monooxygenase (SM), enzyme involved in the conversion of squalene to 2,3(S)-mono-oxidosqualene (MOS), a precursor of lanosterol
Summary
Cholesterol is an important cellular molecule involved in the maintenance of membrane permeability and fluidity, and in the modulation of transmembrane signaling pathways, as well as in the synthesis of steroid hormones, bile acids and vitamin D [1,2,3]. The resulting cholesteryl with a into fatty chylomicrons acid in a process mediated by acyl-cholesterol acyl transferase (ACAT2), an ester isesterified incorporated and delivered to the Golgi apparatus for further processing enzyme localized in the membrane of the reticulum [9].amount and secretion to the circulation through theendoplasmic thoracic duct [10]. Small of free cholesterol is ester is incorporated into chylomicrons and delivered to the Golgi apparatus for further processing excreted back into the intestinal lumen by apical transporters, such as ATP-binding cassette transporters and secretion to the circulation through the thoracic duct [10]. LXR canABCG5/G8 induce ABCA1-mediated cholesterol efflux toback prevent cholesterol in the and activate inducing cholesterol excretion to the lumen.accumulation. LXR can induce enterocytes. cholesterol efflux to prevent cholesterol accumulation in the enterocytes
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