Understanding the Disorders of High-Density Lipoprotein Metabolism

What Is Lipoprotein?

• Lipoproteins are proteins that carry triglycerides and cholesterol that travel in the bloodstream throughout the body. Since triglycerides and cholesterols are not soluble in water, they are transported in association with proteins. They are complex molecules containing triglycerides and cholesterol esters surrounded by apolipoproteins, phospholipids, and free cholesterol that facilitate lipoprotein function.

• The central core of lipids is made up of non-polar lipids that are primarily made up of triglycerides and cholesterol esters.

• Low-density cholesterol (LDL) is considered good cholesterol, and high-density cholesterol (HDL) is considered bad cholesterol. The lipoproteins carry cholesterol and triglycerides throughout the body.

• Cholesterol is also a type of lipid that builds up in the heart's blood vessels, leading to heart disease. To prevent cardiovascular diseases, the overall HDL levels should be higher than LDL levels because HDL helps to remove LDL and reduces the risk of heart diseases.

• Lipoproteins comprise a core of cholesterol and triglycerides and are spherical molecules. There are seven types of cholesterol, and they are low-density lipoproteins (LDL), high-density lipoproteins (HDL), intermediate-density lipoproteins (IDL), chylomicrons, chylomicron remnants, very low-density lipoproteins and intermediate-density lipoproteins which are large and triglyceride-rich lipoproteins that produce dietary fats.

• The functions of lipoproteins in the body are transporting the lipids from the liver to the tissues, transferring the lipids from the tissues to the liver, and absorption and transport of lipids in the small intestine.

What Are High-Density Lipoproteins?

High-density cholesterols are good cholesterols because they absorb and carry the cholesterol from the blood and transport it to the liver. The liver flushes out the cholesterols from the body. This mechanism of HDL prevents the accumulation of cholesterol in the body, reducing the risk of atherosclerosis (a condition where there is a block in the blood flow due to the deposition of cholesterols in the blood vessels supplying the heart). The fibrofatty deposits in the blood vessels are called plaque, which causes health problems like stroke (a condition that occurs due to a block in the blood supply to the brain) and heart disease. The plaque is made up of cholesterols. HDL levels greater than 60 milligrams per deciliter (mg/dL) are considered high, and HDL levels less than 40 mg/dL are considered low.

How Is High-Density Lipoprotein Synthesized?

The liver synthesizes the fat absorbed from the diet and is transported between the various organs and tissues for storage and utilization. The HDLs are synthesized and secreted from the liver as disk-shaped nascent HDL particles that consist primarily of free cholesterol, phospholipids, and apolipoproteins devoid of cholesterol ester and triacylglycerol.

Lecithin cholesterol acyltransferase (LCAT) is an enzyme synthesized by the liver that binds to the nascent HDL. This nascent HDl picks the cholesterol from the lipoproteins, cell membranes, and peripheral tissues. This picked cholesterol is converted into cholesterol esters by the action of LCAT. As the cholesterol in the HDL becomes esterified by the LCAT enzyme, it creates a concentration gradient and draws in free cholesterol from the tissues and other lipoproteins. This spherical HDl that is enriched in cholesterol ester enters the liver. In the liver, the cholesterol esters are degraded to cholesterol, which is utilized to synthesize bile acids and lipoproteins or excreted into bile as cholesterol.

What Is the Significance of Reverse Cholesterol Transport?

It is a process by whichexcess cholesterol contained in the extrahepatic tissues is taken to the liver through the HDL metabolic cycle for the utilization or excretion through the bile. The LCAT esterifies the HDL's cholesterol content, preventing it from re-entering the cells. By reverse cholesterol transport, cellular and lipoprotein cholesterol is delivered back to the liver. The liver is the only organ that removes the excess cholesterol by secreting it in the bile for excretion in the feces. Reverse cholesterol transport prevents the deposition of cholesterols in the tissues, and it prevents atherosclerosis. Elevated HDL cholesterol decreases heart disease.

What Are the Disorders of High-Density Lipoprotein Metabolism?

Elevated levels of HDL are caused by genetic disorders accompanying metabolic and lipid abnormalities. The primary causes of elevated HDL levels are multiple or single genetic mutations that result in overproduction or decreased clearance of HDL. The secondary causes of high HDL levels are:

• Hyperthyroidism (high thyroid hormone secretion in the body).

• Primary biliary cirrhosis (a chronic disease in which the bile ducts in the liver are slowly destroyed).

• Drugs such as Insulin, Estrogen, Corticosteroids, and Phenytoin.

• The disorders of HDL metabolism are cholesteryl ester transfer protein (CETP) deficiency and familial hyper alpha lipoproteinemia.

What Is the Cholesteryl Ester Transfer Protein Deficiency (CETP)?

The cholesterol ester transfer protein is involved in the transfer of cholesteryl esters from the high-density lipoproteins to apolipoprotein B, which contains lipoproteins including VLDL (very low-density lipoprotein), VLDL remnants, and LDLs. The deficiency of cholesterol ester transfer protein is associated with increased high-density cholesterol levels and decreased low-density cholesterol levels.

How to Boost HDL Levels?

HDL is low in people with metabolic syndrome with a cluster of conditions like high blood pressure, obesity, and high glucose levels. Physical activity and exercises lower triglycerides and increase HDL levels. Avoiding processed sugars and transfats can increase HDL levels. Foods such as cookies, cakes, and fried foods contain transfats. Avoiding smoking and alcohol helps to increase HDL levels. Transfats are a type of unsaturated fat that is available in artificial and natural forms.

The foods that have trans fat are:

• Some spread like peanut butter and margarine.

• French fries.

• Pre-prepared and packaged foods like pizza, pie crusts, and cookie dough.

• Donuts, pies, and pastries.

• Fried foods include onion rings, nuggets, and fried chicken.

• Some snack foods such as crackers, cookies, and chips.

One can avoid transfat by taking the following alternatives:

• Naturally occurring oils such as corn oil, olive oil, and canola oil.

• Plant-based meat alternatives.

• Instead of non-diary coffee, almond milk and oat milk can be consumed.

• Monosaturated fats are the fats that are present both in animal products and plant products. One of the examples of monounsaturated fat is olive oil.

• Monounsaturated fatty acids are a type of dietary fat, and it is one of the healthy fats. It is found in plant foods such as nuts, avocados, and vegetable oils.

Conclusion:

High-density lipoproteins are good cholesterols that are required more for the regulation of cholesterol levels in the body. High-density lipoprotein metabolic disorders can disrupt normal metabolism, which causes elevated levels of HDLs. HDL deficiency can be caused by genetic obesity, smoking, and a sedentary lifestyle. Disorders associated with high-density lipoproteins metabolism lead to abnormal levels of HDL that increase the risk of heart disease.