Cholesterol, Triglycerides, and Associated Lipoproteins - Clinical Methods - NCBI Bookshelf
VLDL and Chylomicrons - The Role of Triglyceride-Rich Lipoproteins There is an association between low levels of HDL-C and increased. Whether there is a causal association between blood levels of . index foods and high fructose foods) can lower VLDL and triglycerides. Cholesterol, triglycerides, and high-density lipoproteins are important receptor sites, and intervening in the exchange of lipid constituents between lipoprotein particles. The synthesis and secretion of VLDL at cellular level occur in a process Subclass HDL2 has been reported to have a better correlation with coronary.
Chylomicrons and very low-density lipoprotein VLDL are examples of triglyceride-rich lipoproteins. Triglyceride-Rich Lipoproteins High blood levels of triglycerides are most often associated with high levels of the two most important triglyceride-rich lipoproteins; chylomicrons and VLDL. Chylomicrons are formed in the intestine after a meal. They contain triglycerides and small amounts of cholesterol.
The chylomicron remnants are then removed from the circulation by liver cells. Triglycerides are composed of three molecules of fatty acids attached to a glycerol molecule. Definition of Normal and High Levels of Triglycerides Blood levels of triglycerides are stratified according to population data and their associated risk of coronary artery disease.
Hypertriglyceridemia is a relatively common disorder. In the United States, 33 percent of adults have triglyceride levels above 1.
Triglycerides and Cardiovascular Disease Whether there is a causal association between blood levels of triglycerides and cardiovascular risk is still debated. In other words, it remains uncertain whether high triglycerides cause atherosclerosis. Other conditions associated with high triglycerides, such as insulin resistance, a preponderance of small LDL particles, and low HDL cholesterol, may also play an important causative role when it comes to atherosclerosis.
High concentration of triglyceride-rich lipoproteins is associated with low levels of HDL-cholesterol. This is a result of an exchange of lipids between triglyceride-rich lipoproteins and HDL-cholesterol leading to triglyceride-enriched HDL particles low in cholesterol.
Low levels of HDL cholesterol are known to be associated with increased risk of heart disease Triglycerides may become elevated with obesity, physical inactivity, high-carbohydrate diet, smoking, diseases such as diabetes and renal failure, drugs such as estrogen, tamoxifen and corticosteroids, and genetic disorders familial hypertriglyceridemia, familial combined hyperlipidemia, and familial dysbetalipoproteinemia. There are several types of familial hypertriglyceridemia.
These disorders are associated with increased risk of coronary artery disease 11 which appears independent of cholesterol levels People with very high triglycerides are at risk of acute pancreatitis inflammation of the pancreas which is characterized by abdominal pain, nausea, and vomiting It is important to understand that these lipoproteins also transport cholesterol.
In the capillaries more Exogenous Pathway The exogenous pathway starts with the intestinal absorption of triglycerides and cholesterol from dietary sources. Its end result is the transfer of triglycerides to adipose and muscle tissue and of cholesterol to the liver.
After absorption, triglycerides and cholesterol are re-esterified in the intestinal mucosal cells and then coupled with various apoproteins, phospholipids, and unesterified cholesterol into lipoprotein particles called chylomicrons.
The chylomicrons in turn are secreted into intestinal lymph, enter the bloodstream through the thoracic: At these binding sites the chylomicrons interact with the enzyme lipoprotein lipase, which causes hydrolysis of the triglyceride core and liberation of free fatty acids.
These fatty acids then pass through the capillary endothelial cells and reach the adipocytes and skeletal muscle cells for storage or oxidation, respectively. After removal of the triglyceride core, remnant chylomicron particles are formed. These remnants are cleared from the circulation by binding of their E apoprotein to a receptor present only on the surface of hepatic cells.
The Difference Between VLDL and LDL
Subsequently, the bound remnants are taken to the inside of hepatic cells by endocytosis and then catabolized by lysosomes. This process liberates cholesterol, which is then either converted into bile acids, excreted in bile, or incorporated into lipoproteins originated in the liver VLDL.
Under normal physiologic conditions, chylomicrons are present in plasma for 1 to 5 hours after a meal and may give it a milky appearance. They are usually cleared from the circulation after a hour fast.
Endogenous Pathway The liver constantly synthesizes triglycerides by utilizing as substrates free fatty acids and carbohydrates; these endogenous triglycerides are secreted into the circulation in the core of very-low-density lipoprotein particles VLDL. The synthesis and secretion of VLDL at cellular level occur in a process similar to that of chylomicrons, except that a different B apoprotein B instead of B together with apoproteins C and E intervene in their secretion.
Subsequent interaction of the VLDL particles with lipoprotein lipase in tissue capillaries leads to hydrolysis of the core triglycerides and production of smaller remnant VLDL particles rich in cholesterol esters intermediate-density lipoproteins, IDL and liberation of free fatty acids. Around half of these remnant particles are removed from the circulation in 2 to 6 hours as they bind tightly to hepatic cells.
The rest undergo modifications with detachment of the remaining triglycerides and its substitution by cholesterol esters and removal of all the apoproteins except apoprotein B. Their predominant function is to supply cholesterol to cells with LDL receptors, like those in the adrenal glands, skeletal muscle, lymphocytes, gonads, and kidneys.
The quantity of cholesterol freed from LDL is said to control cholesterol metabolism in the cell through the following mechanisms: Besides the above described route for LDL degradation in extrahepatic sites, a so-called scavenger cell pathway has been described. This consists of cells in the reticuloendothelial system which, by phagocytosis, dispose of the excess concentrations of this lipoprotein in plasma. Transport of High-Density Lipoprotein Cholesterol High-density lipoproteins are a heterogeneous group of macromolecules with different physical properties and chemical components; two subclasses of HDL have been identified HDL2 and HDL3 within which several subspecies have also been demonstrated.
The predomination function of HDL seems to be the reverse transport of cholesterol from different tissues into the liver, where it is eventually removed. Subclass HDL2 has been reported to have a better correlation with coronary artery disease protection than total HDL cholesterol. The serum concentration of HDL and its components derives from various complex intravascular and cellular metabolic events.
VLDL | Triglyceride-Rich Lipoproteins and Remnant Cholesterol
These events include secretion of precursor HDL particles from the liver and small intestine, interaction of these particles with lipids and proteins released during the catabolism of triglyceride-rich lipoproteins, and production of cholesteryl esters the core substance in HDL from the action of lecithin—cholesterol acyltransferase LCATan enzyme that originates in the liver.
This enzyme acts on unesterified cholesterol released into plasma from cellular turnover. The end result is a system that allows the transfer of cholesterol through LDL to peripheral cells and its return to the liver through HDL, and that prevents excessive accumulation of cholesterol in the body. Clinical Significance Cholesterol and triglycerides, like many other essential components of the body, attract clinical attention when present in abnormal concentrations.
Increased or decreased levels usually occur because of abnormalities in the synthesis, degradation, and transport of their associated lipoprotein particles. When hyperlipidemia or hypolipidemia are defined in terms of the class or classes of increased or decreased plasma lipoproteins, the names hyperlipoproteinemia or hypolipoproteinemia are preferentially employed.Nutrition : How to Lower LDL Cholesterol and Triglycerides
Hyperlipoproteinemia is the lipid disturbance of major relevance clinically because of its association with an increased risk of atherosclerotic cardiovascular disease.
Multiple epidemiologic studies have demonstrated that increased levels of plasma total cholesterol and low-density lipoproteins are strongly and directly related to a greater incidence of coronary heart disease.
VLDL – The Role of Triglyceride-Rich Lipoproteins and Remnant Cholesterol
Elevated plasma triglycerides and very-low-density lipoproteins are directly associated with the risk of atherosclerotic heart disease, although not as independent risk factors. In contrast, high levels of high-density lipoprotein cholesterol have been found to be a protective factor for the development of that disease, so that decreased levels constitute a risk factor.
Clinical manifestations of hyperlipoproteinemia include a greater incidence of ischemic vascular disease, acute pancreatitis, and visible accumulations of lipid deposits xanthomas and xanthelasmas. The localization of these lesions is of great help in many instances to categorize the lipoprotein dysfunction present.
Increased concentration of plasma lipids is etiologically related mainly to genetic disorders, dietary factors such as ingestion of excessive calories, saturated fatty acids and cholesterolor ingestion of drugs, or it may occur as a secondary phenomenon in a large variety of diseases.
In any of these instances the elevation of the different plasma lipoproteins usually occurs in a number of combinations that have led to their classification into six different patterns or phenotypes Table Genetic or acquired disorders may be related to one or more of these lipoprotein patterns, so the identification of a particular pattern gives no specific information regarding the cause of the hyperlipidemic disorder in question. A practical approach is to classify the different hyperlipidemic: In each of these categories primary genetic as well as secondary disorders are included.
The genetic disorders in turn could result from a single gene disturbance either of dominant or recessive inheritance, or a polygenic derangement in which multiple genes interact with environmental factors.