Lipid Metabolism and Associated Disorders

Normal and Abnormal Processing of Cholesterol and Other Fats

May 3, 2009 Anthony Lee

How are the different types of lipids metabolized in the body? How do abnormal lipid conditions occur?

Lipids refer to the molecules of fat, such as cholesterol, triglycerides, and phospholipids, that serve various functions in the human body. Of the different types of lipids, cholesterol and triglycerides are frequently implicated in heart disease, stroke, and other medical conditions. An understanding of lipid metabolism in the body can shed light on the rationale behind health guidelines that recommend keeping blood levels of cholesterol and triglycerides under control.

Lipid Metabolism

In order for lipids to travel through the aqueous environment of the bloodstream, they require proteins called apolipoproteins that combine with lipids. The resulting protein-lipid aggregates, called lipoproteins, are processed in in several distinct steps that are described as follows:

Chylomicrons: Fats ingested through meals are broken down in the gastrointestinal tract and repackaged into chylomicrons, which are combinations of triglycerides, cholesterol, other lipids and apolipoproteins C-II and E. When chylomicrons reach muscle and fat (adipose) tissue, apo C-II triggers the enzyme lipoprotein lipase along the blood vessels to break down triglycerdies for use by local tissues.

Very Low Density Lipoproteins (VLDL): Besides dietary intake, triglyceridea and cholesterol are also synthesized in the liver. They are packaged with apolipoproteins B-100, C-II, and E to form VLDL. Like chylomicrons, VLDL travels through the bloodstream, reaches muscle and adipose tissue, and activates lipoprotein lipase along the blood vessels to break down triglycerides that are taken up by tissues.

Intermediate Density Lipoproteins (IDL): IDL is the cholesterol-rich lipoprotein that results when chylomicrons and VLDL have triglycerides extracted. They return to the liver, which either takes up the lipoprotein or removes additional triglycerides to form low density lipoproteins.

Low Density Lipoproteins (LDL): LDL has the greatest concentration of cholesterol of all the lipoproteins. It circulates in the blood until the liver or other cells with receptors for LDL absorb the lipoprotein. If the amount of cholesterol and fat in the bloodstream is high, fewer LDL receptors are available to accept the lipoprotein, prolonging the time LDL stays in circulation. If the amount of blood cholesterol and fat is low, more LDL receptors are available.

High Density Lipoproteins (HDL): HDL is a lipoprotein that is made by intestinal and liver cells. It initially contains apolipoprotein A-I and no cholesterol, functioning to collect cholesterol as it circulates in the bloodstream. HDL takes this cholesterol to cells that need it and ultimately returns to the liver.

Abnormal Lipid Conditions

The preceding description of lipid metabolism relates to abnormal blood lipid levels, or dyslipidemia (which includes hyperlipidemia), and clinical guidelines to keep them under control. These associations are detailed below according to the specific lipoprotein:

LDL: LDL is the lipoprotein that underlies the arterial plaques of atherosclerosis and, therefore, is referred to as "bad cholesterol." Because increased amounts of fat in the blood reduce the number of LDL receptors that allow cells to clear the lipoprotein from the blood, clinical guidelines recommend a low-fat low-cholesterol diet to keep LDL levels within normal limits.

HDL: Because HDL functions to clear peripheral tissues of cholesterol, it reduces the risk of atherosclerosis and is known as "good cholesterol." Therefore, low HDL levels increase the risk of atherosclerosis and cardiovascular disease. Methods to raise HDL include exercise, weight control, and, if necessary, medications such as niacin.

Triglycerides: Elevated triglycerides in the blood are related to cardiovascular disease. Though it is not clear if the triglycerides themselves directly cause cardiovascular disease or correlate with factors that do, guidelines nevertheless recommend a healthy low-fat diet.

References

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Lipids