Cholesterol and Lipid Metabolism

Dec 23, 2009Updated 8 months ago

Triglyceride Molecule Related to Heart Disease
Lipids are fats that are either absorbed from food or that are manufactured in the liver. All lipids are important for normal physiologic function, but some – cholesterol and triglycerides, for example – may cause problems w hen they are present in large amounts.

With so much attention on the adverse effects of lipids on human health, it is easily forgotten that these molecules play a vital role in day-to-day cellular activities.

Cholesterol, for example, is a major constituent of cell membranes, nervous tissue, steroid hormones (androgens and estrogens), bile acids, and various signaling molecules. Its ubiquitous presence attests to its importance in maintaining good health.

Triglycerides provide a way for the body to transport energy molecules (fatty acids) from one place to another and as an efficient means to store energy in fat and muscle cells.

So, given that lipids are not just bad actors on the stage of human affairs, it is useful – especially for people whose doctors have expressed concern about “high lipid levels” – to know where lipids come from and (more importantly) how they affect our health.

The Role of Diet in Lipid Levels

Ove r 95% of all dietary lipids come in the form of triglycerides. The rest are free fatty acids, cholesterol, phospholipids, and fat-soluble vitamins. Much of the cholesterol found in human tissues is not directly acquired from the diet but is synthesized within the body; free fatty acids derived from dietary triglycerides serve a role in cholesterol production.

A triglyceride molecule is composed of a three-carbon backbone with a fatty acid chain attached to each of the carbon atoms. This structure provides an efficient carrier for fatty acids, which are important energy molecules and which form the basis for manufacturing other types of molecules.

Triglycerides obtained from foods are digested in the stomach and duodenum into monoglycerides (a three-carbon backbone with a single fatty acid attached) and free fatty acids (FFAs). Dietary cholesterol esters – the form of cholesterol commonly found in foods – are converted to free cholesterol.

Monoglycerides , FFAs, and free cholesterol are emulsified by bile acids and shuttled to the intestinal villi where they are absorbed by cells lining the digestive tract. Once inside the intestinal cells, FFAs and monoglycerides are converted back into triglycerides, and the triglycerides and cholesterol are packaged with proteins (lipoproteins) to form chylomicrons.

Chylomicrons and other lipoproteins make it possible for lipids, which are not soluble in water, to be transported through the bloodstream and into cells where the lipids can do their work.

Lipoproteins Define the Structure and Function of Lipid Molecules

Lipoproteins are a broad class of specialized proteins that surround lipid molecules and carry them through the body. Lipoproteins themselves possess surface proteins that attach to specific cellular receptors or that bind to lipid-processing enzymes. Lipoproteins are further classified by their size and the nature of their surface proteins:

  • Chylomic rons: The largest of all lipoproteins, chylomicrons package triglycerides and cholesterol and transport them from the intestine, where they are absorbed, into the circulation. Chylomicrons are “chopped up” in fat and muscle tissue, where most of their triglyceride content is used for energy or stored; cholesterol-laden chylomicron remnants then return to the liver for further processing.
  • Low-density lipoproteins (LDL): These lipoproteins contain more cholesterol than any other class, having been constructed in the liver from chylomicron remnants and other cholesterol-rich lipoproteins. Once in the circulation, LDL attaches to receptors on cells that inhabit the lining of blood vessels; oxidized LDL within these cells contributes to the inflammatory process that leads to plaque formation on vascular walls and, eventually, to atherosclerosis and cardiovascular disease.
  • High-density lipoproteins (HDL): Formed within cells in the gut and the liver, HDLs are i nitially cholesterol-free lipoproteins that – much like empty dump trucks – travel from their points of origin to peripheral tissues where they “scoop up” cholesterol and carry it to other tissues where it can be used for metabolism or broken down and cleared. HDL, then, tends to carry cholesterol away from vascular plaques, thus helping to prevent atherosclerosis.
Although several other lipoproteins that affect human health have been described, it is easy to see why high triglyceride and LDL levels are associated with cardiovascular disease. Likewise, the role of a high HDL in attenuating the effects of atherosclerosis is clear. While there is no clear-cut division between normal and abnormal lipid levels, years of research and experience (see Framingham Heart Study) have contributed inf ormation that helps physicians to identify people who are at risk for strokes, heart attacks, and other conditions related to abnormal lipid levels.


Lipid Disorders in Endocrine and Metabolic Disorders. The Merck Manual, 18th Edition. 2006:1295-6