Two main pathways are involved in the intravascular transport of lipids in the form of lipid-apoprotein complexes called lipoproteins (Ye and Kwiterovich, 2000). The first endogenous pathway controls parameters that can be measured at fasting: the liver produces and secretes very low-density lipoproteins (VLDL) bearing apoproteins apoB-100, apoE, apoCII and apoCIII. Triglycerides, then phospholipids, are hydrolysed by endovascular lipoprotein lipase and hepatic lipase, to large intermediate density lipoproteins (IDL), then to small remnants known as low-density lipoproteins (LDL), which are enriched in cholesterol and which, owing to their longer half-life, tend to accumulate in the circulation.
The second pathway can be referred to as 'exogenous' and originates from the digestion and absorption in the gut of dietary fat provided by meals. The absorptive enterocyte secretes into the bloodstream large triglyceride-rich lipoproteins, which contain apoB-48, apoAl, apoA-IV, then apoE, apoCII and apoCIII. This results in the transient accumulation of postprandial chylomicrons, from which triglycerides and phospholipids are progressively withdrawn by the combined activity of lipoprotein and hepatic lipases. This generates smaller chylomicron remnants in a few hours. Endogenous and exogenous remnants are then cleared from the circulation thanks to receptor-driven mechanisms, i.e. liver apoB,E and remnant receptors or peripheral tissue apoB,E receptor and scavenger receptor.
Circulating high-density lipoproteins (HDL) bearing apoAl and apoAII can exchange lipids with VLDL. Chylomicrons, through the transfer activity of cholesterol esters, transfer protein (CETP) or phospholipid transfer protein (PLTP) and ensure the reverse cholesterol transport to the liver through the scavenger receptor type I (SR-BI). Within liver and intestine cells, the production of VLDL or chylomicrons is controlled by the action of specific proteins such as fatty acid binding proteins (FABPs) and the microsomal transfer protein (MTP).
Two major genetic defects are known to dramatically affect lipoprotein metabolism. The most famous is the defect in apoB,E-receptor that induces familial hypercholesterolaemia and elevated LDL levels (Brown and Goldstein, 1974). The second one is the defect in MTP that almost completely abolishes triglyceride-rich lipoprotein (TRL) production by the liver and small intestine resulting in abetalipoproteinaemia (Gregg and Wetterau, 1994). Such marked and rare genetic defects are not within the scope of the present review, the aim of which is to provide some examples of common gene polymorphisms that may have implications for large proportions of the population, especially in determining variation in response to dietary fat.
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