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. 2023 Jun 29;12(13):4399. doi: 10.3390/jcm12134399

Figure 4.

Figure 4

Putting together TRL fluxes: general outline of endogenous and exogenous TRL turnover. (1) Endogenous TRLs coming from the liver as well as, in the postprandial phase, exogenous TRLs coming from the intestines, are protagonists of a series of complex reactions and transfers of proteins and lipids in the circulation. The main physiological pathway is to deliver fatty acids to the tissues in need in a regulated fashion. Both TRL species undergo lipolysis by lipoprotein lipase, but chylomicrons are the preferred substrate. It must be emphasized that VLDL production occurs throughout the day. Therefore, an excess of chylomicrons may result in the accumulation of VLDLs. (2) Under the action of LPL, VLDL and chylomicrons are considerably reduced in size and the excess phospholipids and cholesterol are transferred to HDL. HDL plays a key role in the metabolism of TRL because it also provides many of the surface apolipoproteins that are significant actors in this process. Cholesterol-ester transfer protein (CETP) plays a very important role in the transfer of esterified cholesterol from HDLs from VLDLs and chylomicron particles as well as receiving TGs from these molecules, which passes to HDLs. (3) The resulting partially delipidated molecules become enriched in cholesterol esters and are called remnants. (4) In the case of VLDLs, an intermediate remnant is called an IDL or intermediate density lipoprotein that ultimately is delipidated into LDL, which loses the surface apolipoproteins and contains only apoB100 and apoE. (5) When this delicate process is perturbed and there are delays in intravascular catabolism, some of the remnants are substrates for very active hepatic and endothelial lipases and the final product is small-dense LDL, which is far more atherogenic than large buoyant LDL. (6) TRL remnants are taken up by the liver via several receptors, as we show in the figure: LDL receptor, LDL receptor like-protein1, scavenger receptor B1, and syndecan 1. This is the pathway by which dietary liposoluble vitamins and cholesterol finally reach the liver, in the form of chylomicron remnants. (7) Delays in any part of this process result in the transfer of the TRL remnants into the arterial intima. Remnants are less abundant but contain twice as much cholesterol esters as LDL and are equally or more atherogenic. The figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.