4.71 Lipoproteins

Lipoproteins, as the name suggests, are complexes of lipids and protein. The proteins within a lipoprotein are called apolipoproteins (aka apoproteins). There are a number of different apolipoproteins that are abbreviated apo-, then an identifying letter (i.e. Apo A) as shown in the chylomicron below.

Figure 4.711 Chylomicron structure1

The following video does a nice job of illustrating the different lipoprotein components.

Web Link

Video: Lipoproteins (0:28)

There are a number of lipoproteins in the body. They differ by the apolipoproteins they contain, size (diameter), density, and composition. The table below shows the difference in density and diameter of different lipoproteins. Notice that as diameter decreases, density increases.

Table 4.711 The density and diameter of different lipoproteins2

Lipoprotein Density (g/dL) Diameter (nm)
Chylomicrons 0.95 75-1200
VLDL (very low-density lipoproteins) 0.95-1.006 30-80
IDL (intermediate-density lipoproteins) 1.006-1.019 25-35
LDL (low-density lipoproteins) 1.019-1.063 18-25
HDL (high-density lipoproteins) 1.063-1.21 5-12

This inverse relationship is a result of the larger lipoproteins being composed of a higher percentage of triglyceride and a lower percentage of protein as shown below.

Figure 4.712 Composition of lipoproteins3

Protein is more dense than triglyceride (why muscle weighs more than fat), thus the higher protein/lower triglyceride composition, the higher the density of the lipoprotein. Many of the lipoproteins are named based on their densities (i.e. very low-density lipoproteins).

As described in the last subsection, the lipoproteins released from the small intestine are chylomicrons. The video below does a nice job of showing, describing, and illustrating how chylomicrons are constructed and function.

Web Link

Video: Chylomicrons (0:55)

The endothelial cells that line blood vessels, especially in the muscle and adipose tissue, contain the enzyme lipoprotein lipase (LPL). LPL cleaves the fatty acids from lipoprotein triglycerides so that the fatty acids can be taken up into tissues. The figure below illustrates how endothelial cells are in contact with the blood that flows through the lumen of blood vessels.

Figure 4.713 Lining of a blood vessel. The lumen is where the blood would be flowing, thus endothelial cells are those that are in contact with blood4

LPL cleaves fatty acids from the triglycerides in the chylomicron, decreasing the amount of triglyceride in the lipoprotein. This lipoprotein with less triglycerides becomes what is known as a chylomicron remnant, as shown below.

Figure 4.714 The cleavage of triglycerides by LPL from a chylomicron leads to the formation of a chylomicron remnant.

Now in the form of a chylomicron remnant, the digested lipid components originally packaged into the chylomicron are directed to the liver where the chylomicron remnant is endocytosed. This process of clearing chylomicrons from the blood takes 2-10 hours after a meal2. This is why people must fast 12 hours before having their blood lipids (triglycerides, HDL, LDL etc.) measured. This fast allows all the chylomicrons and chylomicron remnants to be cleared before blood is taken. However, whether patients should be asked ot fast has been questioned as described in the link below.

Web Link

Should you fast before a cholesterol test?

After the chylomicron remnant is endocytosed, it is broken down to its individual components (triglycerides, cholesterol, protein etc.). In the liver, VLDL are produced, similar to how chylomicrons are produced in the small intestine. The individual components are packaged into VLDL and secreted into circulation as shown below.

Figure 4.715 Chylomicron remnants are taken up by the liver. The liver secretes VLDL that contain cholesterol (C)

Like it does to chylomicrons, LPL cleaves fatty acids from triglycerides in VLDL, forming the smaller IDL (aka VLDL remnant). Further action of LPL on IDL results in the formation of LDL. The C in Figures 4.715 and 4.716 represents cholesterol, which is not increasing; rather, since triglyceride is being removed, it constitutes a greater percentage of particle mass of lipoproteins. As a result, LDL is composed mostly of cholesterol, as depicted in the figure below.

Figure 4.716 Formation of IDL and LDL from VLDL

LDL contains a specific apolipoprotein (Apo B100) that binds to LDL receptors on the surface of target tissues. The LDL are then endocytosed into the target tissue and broken down to cholesterol and amino acids.

HDL are made up of mostly protein and are derived from the liver and intestine. HDL participates in reverse cholesterol transport, which is the transport of cholesterol back to the liver. HDL picks up cholesterol from tissues/blood vessels and returns it to the liver itself or transfers it to other lipoproteins returning to the liver.

Figure 4.717 HDL is involved in reverse cholesterol transport

The animation under the transport button in the following link does a really nice job of going through the process of lipoprotein transport.

Web Link

Lipoprotein Animation

You are probably familiar with HDL and LDL being referred to as “good cholesterol” and “bad cholesterol,” respectively. This is an oversimplification to help the public interpret their blood lipid values, because cholesterol is cholesterol; it’s not good or bad. LDL and HDL are lipoproteins, and as a result you can’t consume good or bad cholesterol, you consume cholesterol. A more appropriate descriptor for these lipoproteins would be HDL “good cholesterol transporter” and LDL “bad cholesterol transporter.”

What’s so bad about LDL? LDL enters the endothelium where it is oxidized. This oxidized LDL is engulfed by white blood cells (macrophages), leading to the formation of what are known as foam cells. The foam cells eventually accumulate so much LDL that they die and accumulate, forming a fatty streak. From there the fatty streak, which is the beginning stages of a lesion, can continue to grow until it blocks the artery. This can result in a myocardial infarction (heart attack) or a stroke. HDL is good in that it scavenges cholesterol from other lipoproteins or cells and returns it to the liver. The figure below shows the formation of the fatty streak and how this can progress to a point where it greatly alters blood flow.

Figure 4.718 The formation of a lesion in an artery5

The video below does an excellent job of illustrating this process. However there are two caveats to point out. First, it incorrectly refers to cholesterol (LDL-C etc.), and second, it is clearly made by a drug company, so keep these factors in mind. The link below is the American Heart Association’s simple animation of how atherosclerosis develops.

Web Link

Video: Atherosclerosis (5:36)

Cholesterol and CAD

Web Link

Doubt Cast on the ‘Good’ in ‘Good Cholesterol’

Study Questions Fat and Heart Disease Link

The following video gives a general overview of macronutrient digestion, uptake, and absorption.

Web Link

Video: Small Intestine (1:29)

References & Links

1. http://en.wikipedia.org/wiki/File:Chylomicron.svg

2. Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s perspectives in nutrition. New York, NY: McGraw-Hill.

3. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.

4. http://en.wikipedia.org/wiki/File:Anatomy_artery.png

5. 7. Erdman JW Jr., MacDonald IA, Zeisel SH, editors. (2012) Present knowledge in nutrition – 10th ed. Ames, IA: Wiley-Blackwell.

6. http://en.wikipedia.org/wiki/File:Endo_dysfunction_Athero.PNG

Links

Ask Well: Should you fast before a cholesterol test – http://well.blogs.nytimes.com/2016/05/24/ask-well-should-you-fast-before-a-cholesterol-test/

Lipoprotein Animation – http://www.wiley.com/legacy/college/boyer/0470003790/animations/cholesterol/cholesterol.swf

Cholesterol and CAD – http://watchlearnlive.heart.org/CVML_Player.php?moduleSelect=chlcad

Doubt Cast on the ‘Good’ in ‘Good Cholesterol’ – http://www.nytimes.com/2012/05/17/health/research/hdl-good-cholesterol-found-not-to-cut-heart-risk.html

Study Questions Fat and Heart Disease Link – http://well.blogs.nytimes.com/2014/03/17/study-questions-fat-and-heart-disease-link/

Videos

Lipoproteins – https://www.youtube.com/watch?v=x-4ZQaiZry8

Chylomicrons – http://www.youtube.com/watch?v=hRx_i9npTDU

LDL Receptor – http://www.youtube.com/watch?v=XPguYN7dcbE

Atherosclerosis – http://www.youtube.com/watch?v=fLonh7ZesKs&feature=rec-HM-r2

Small Intestine – http://www.youtube.com/watch?v=P1sDOJM65Bc