VLDL - very-low-density lipoprotein

Fibric acid derivatives, the third group of antihyperlipi-demic drugs, work in a variety of ways. Clofibrate (Atromid-S), acts to stimulate the liver to increase breakdown of very-low-density lipoproteins (VLDL) to low-density lipoproteins (LDL), decreasing liver synthesis of... 

Figure 25-4. Metabolic fate of very low density lipoproteins (VLDL) and production of low-density lipoproteins (LDL). (A, apolipoprotein A B-100, apolipoprotein B-100 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylglycerol IDL, intermediate-density lipoprotein C, cholesterol and cholesteryl ester P, phospholipid.) Only the predominant lipids are shown. It is possible that some IDL is also metabolized via the LRP.

Figure 25-6. The synthesis of very low density lipoprotein (VLDL) in the liver and the possible loci of action of factors causing accumulation of triacylglycerol and a fatty liver. (EFA, essential fatty acids FFA, free fatty acids ...

Four major groups of lipoproteins are recognized Chylomicrons transport lipids resulting from digestion and absorption. Very low density lipoproteins (VLDL) transport triacylglycerol from the liver. Low-density lipoproteins (LDL) deliver cholesterol to the tissues, and high-density lipoproteins (HDL) remove cholesterol from the tissues in the process known as reverse cholesterol transport. 

This approach can be used only for fat-soluble compounds that follow the same lymphatic route to be transported to the liver as carotenoids. The bioavailability of the compound of interest is determined by monitoring the appearance of the compound and its newly formed intestinal metabolites in the postprandial chylomicron fraction of plasma [also called the density < 1.006 kg/L fraction or triglyceride-rich lipoprotein (TRL) fraction because it is generally a mixture of chylomicrons (CMs) and very low density lipoproteins (VLDLs)] as a function of the time after ingestion. 

TAG-CH3 and TAG-CH2-, acyl chain terminal-CH3 and bulk (-CH2-)n groups, respectively, of fatty acids (predominantly triacylglycerols) associated with chylomicron- and very low-density lipoprotein (VLDL) Thr, threonine-CHs Val, valine-CHs. The asterisk In spectrum (b) denotes a radiolytically-generated 2.74 p.p.m. 

Antibodies to very low density lipoprotein (VLDL) and LDL have been detected in the serum of patients with RA, but not control groups (Lazarevic et al., 1993). In these studies, 38% of patients with active RA tested positive for anti-VLDL/LDL antibodies whilst these autoantibodies were not detected in patients with psoriatic arthritis, osteoarthritis or healthy subjects. Lipoproteins were found in the dissociated components of circulating immune complexes in the serum of 30% of the RA patients. It was concluded that dyslipoproteinaemia in some RA patients may be due to an autoimmune component of the disease. 

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

In the enterocyte, provitamin A carotenoids are immediately converted to vitamin A esters. Carotenoids, vitamin A esters, and other lipophilic compounds are packaged into chylomicrons, which are secreted into lymph and then into the bloodstream. Chylomicrons are attacked by endothelial lipoprotein lipases in the bloodstream, leading to chylomicron remnants, which are taken up by the liver (van den Berg and others 2000). Carotenoids are exported from liver to various tissues by lipoproteins. Carotenes (such as (3-carotene and lycopene) are transported by low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), whereas xanthophylls (such as lutein, zeax-anthin, and (3-cryptoxanthin) are transported by high-density lipoproteins (HDL) and LDL (Furr and Clark 1997). 

Several clinical studies revealed that administration of fenofibrate produces reductions in total-C, LDL-C, apo B, total triglycerides, and triglyceride-rich (very low density) lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in HDL-C, apo AI, and apo AIL However, since fenofibrate is rapidly converted to fenofibric acid during absorption and fenofibric acid, but not fenofibrate, is found circulating in plasma, the effects of fenofibric acid have been extensively evaluated in these studies. 

The specific mechanism by which chlordecone is transferred from the gut, lungs, or skin to the blood is not known. However, the preferential distribution of chlordecone to the liver rather than the fat tissues suggests that it may be transported in the plasma differently from other organochlorine compounds (Soine et al. 1982). In vitro and in vivo studies of human, rat, and pig plasma showed that chlordecone is preferentially bound by albumin and high-density lipoproteins (HDL), which may explain its tissue distribution. Other organochlorine pesticides such as aldrin and dieldrin bind to very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) and distribute preferentially to fat (Soine et al. 1982). 

Very low density lipoprotein (VLDL) 90 40-80 10-40 15-20 5-10 Transport of fat synthesized in the liver (endogenous triacylglycerol)... 

Lp(a), moving, like very low-density lipoproteins (VLDL), in the pre-(3,-lipoprotein fraction upon electrophoresis (B8, B9), but not floating like VLDL in ultracentrifugation (H29), partly resembles low-density lipoprotein (LDL). Its protein moiety consists of one glycoprotein molecule, named apolipoprotein (a)... 

Details of plasma lipoproteins and their metabolism are given in Section 5.5. Most of the cholesterol in the blood is carried as part of low density lipoprotein (LDL) or high density lipoprotein (HDL), whereas most triglyceride, in the fasting state, is carried by very low density lipoprotein (VLDL). The relative concentrations of these lipoproteins constitute the lipid profile and determine CVD risk. Diabetics are more likely to show an unhealthy profile with elevated concentrations of LDL and triglyceride but reduced HDL concentration. This pattern can be partly explained by enhanced fatty acid liberation from adipocytes as a consequence of insulin resistance in that tissue and due to reduced removal from the circulation of triglycerides, which is also insulin dependent. 

High-density lipoproteins (HDL) and very low-density lipoproteins (VLDL) are synthesized in the liver. LDL is produced in the blood stream as VLDL particles are partially delipidated by lipoprotein lipase, a triglyceride hydrolysing enzyme located on the luminal surface of vessels in sites such adipose tissue. 

Liver sends triglycerides to adipose tissue packaged as very low-density lipoproteins (VLDL reviewed later in this chapter). A small amount of triglyceride may be stored in the liver. Accumulation of significant triglyceride in tissues other than adipose tissue usually indicates a pathologic state. 

The resulting triacylglycerol is stored in adipose tissue. In the liver, some is combined with protein and phospholipids to form a complex, known as very low density lipoprotein (VLDL), which is secreted from the liver into the blood. Details of the formation of VLDL are presented in Appendix 11.2. Failure to form VLDL or secrete can cause accu-... 

The liver forms increased amounts of glycogen and fats from the substrates supplied. Glycogen is stored, and the fat is released into the blood in very low density lipoproteins (VLDLs). 

Lipid metabolism in the liver is closely linked to the carbohydrate and amino acid metabolism. When there is a good supply of nutrients in the resorptive (wellfed) state (see p. 308), the liver converts glucose via acetyl CoA into fatty acids. The liver can also take up fatty acids from chylomicrons, which are supplied by the intestine, or from fatty acid-albumin complexes (see p. 162). Fatty acids from both sources are converted into fats and phospholipids. Together with apoproteins, they are packed into very-low-density lipoproteins (VLDLs see p.278) and then released into the blood by exocytosis. The VLDLs supply extrahepatic tissue, particularly adipose tissue and muscle. 

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