OK, here's an attempt at lipidology. Check my math!
Hallow particles which transport non-water soluble substance in the blood include the apolipoprotein particles.
The cargo of each type differs. For example, fatty substances from the diet are picked up and transported throughout the body by chylomicrons. The liver produces other fatty substances and packages them into very low density lipoprotein vLDL particles - which can be converted to LDL along the way. The particles carrying cargo to the body have protein "address labels" on their surface. Each different label gets a letter. In this case the shared address label is apoprotein B. It binds the a family of LDL receptors (LDLr) on "hungry" cells and the passing particles are engulfed into these cells.
Each apolipoprotein type has a different size, density, and carries different %s of different cargos. They also have different tendencies to stick to and slip into vessel walls - causing atheroslerosis.
In the body:
Chylomicrons contain about 90% triglycerides and only 3% cholesterol. (from your gut)
vLDL contain about 70% triglycerides (from the liver)
LDL contains only 10% triglycerides and about 26% cholesterol (from conversion of vLDL, when the package contains are tinkered with and a new address label is added to forward the package along to the next stop; this is "bad cholesterol")
HDL, which carries cargo in the opposite direction - from body systems back to the liver has a different address label protein, of course. This is "reverse cholesterol transport". In this case it requires apoA. HDL cargo is about 5% triglycerides. This is "good cholesterol".
So if cells lack LDL family-receptors the cells can't bind to and take up chylomicrons, vLDL, or LDL as effectively. And both cholesterol and triglyceride levels can go up, because the particles remain in the blood.
High levels of old LDL allows opportunities for lipid oxidation and atherosclerosis.
In the brain:
These particles don't generally pass the blood-brain-barrier. Instead all brain cholesterol etc. is made inside the brain, mostly by astrocytes. These particles are slightly different then those circulating in the body. Some of the address labels are different, for example. But those hungry brain cells still use LDL receptors to bind to them and engulf them. So a lack of these receptors presumable could create a similar scenario in the brain. The cells can't take up the substances they need, and they float around.
So, if you "fix" the receptors hungry cells get fed and circulating levels of all cargo types go down.
It's way more complicated and I struggle to understand it all but.....I think this is basically right. It's good to keep in mind that triglycerides and phospolipids can be broken done into three or two fatty acid chains and then rebuilt inside cells. So free fatty acid cargo and triglyceride cargo can be interchangeable at some points.
Ironically, apoE is one of these protein address labels, on vLDL and intermediate density lipoprotein particles (IDL) in the blood and on some particles inside of the brain. So apoe4 - the protein - gets around easily outside of inside of cells - and into the nucleus, surprisingly. The shape of apoe2 and 3 work well to form good, strong lipoprotein particles for cargo transport. Apoe4 has a kink, causing the particles to be poorly shaped and less effective at carrying cargo.....and apoe4 binds poorly to LDL receptors for uptake, it co-binds with AB, and it sneaks into the nucleus to alter the expression of 100s or 1000s of genes.
Sorry, that got long. Basically, cholesterol and triglycerides are often co-transported. So a malfunction in the uptake system leaves both doing laps throughout the circulatory system.
Staiva? MarkR? Did I get that right?
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