Cholesterol, lipoproteins and the liver
Blood levels of LDL cholesterol (LDL-C) are often assessed when evaluating the Many studies have shown a strong and graded correlation between LDL-C. Most of the cholesterol in the blood is carried in LDL, so your total cholesterol level is usually a reflection of the amount of LDL cholesterol in. LDL (low-density lipoprotein), sometimes called “bad” cholesterol, makes up most of your body’s cholesterol. High levels of LDL cholesterol raise your risk for heart disease and stroke. HDL (high-density lipoprotein), or “good” cholesterol, absorbs cholesterol and carries.
Usually this replacement is obtained from dietary sources, but another portion is synthesized in multiple cells of the body. Triglycerides are also obtained from the diet as well as synthesized by the liver. The origin of circulating lipoproteins is less understood than is their uptake, transport, and degradation.
The lipid transport system in plasma has been described as involving two pathways: Exogenous and endogenous fat-transport pathways are diagrammed. Dietary cholesterol is absorbed through the wall of the intestine and is packaged, along with triglyceride glycerol ester-linked to three fatty acid chainsin chylomicrons. 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. 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.HDL Cholesterol & Heart Disease Risk
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.
HDL (Good), LDL (Bad) Cholesterol and Triglycerides | American Heart Association
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. 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.
Cholesterol, Lipoproteins and the Liver
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.
Hyperlipoproteinemia is the lipid disturbance of major relevance clinically because of its association with an increased risk of atherosclerotic cardiovascular disease.
LDL Cholesterol - The "Bad" Cholesterol Explained
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.
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. Saturated fat and cholesterol in the food you eat make your blood cholesterol level rise. Saturated fat is the main problem, but cholesterol in foods also matters.
Reducing the amount of saturated fat in your diet helps lower your blood cholesterol level. Foods that have high levels of saturated fats include some meats, dairy products, chocolate, baked goods, and deep-fried and processed foods. Being overweight is a risk factor for heart disease.
It also tends to increase your cholesterol.
Losing weight can help lower your LDL bad cholesterol, total cholesterol, and triglyceride levels. It also raises your HDL good cholesterol level. Not being physically active is a risk factor for heart disease. It also helps you lose weight.
LDL and HDL Cholesterol: "Bad" and "Good" Cholesterol
You should try to be physically active for 30 minutes on most, if not all, days. Cigarette smoking lowers your HDL good cholesterol. HDL helps to remove bad cholesterol from your arteries. So a lower HDL can contribute to a higher level of bad cholesterol. Things outside of your control that can also affect cholesterol levels include: As women and men get older, their cholesterol levels rise. Before the age of menopause, women have lower total cholesterol levels than men of the same age.
After the age of menopause, women's LDL bad cholesterol levels tend to rise.
Your genes partly determine how much cholesterol your body makes. High blood cholesterol can run in families.