Cholesterol and Fat Metabolism, Lipid Transport, and Lipoproteins
How fats are digested and/or produced, then distributed - a deep dive on Chylomicrons, VLDL, IDL, LDL, HDL, and more.
O.K., so pretty much anyone alive over the last few decades has probably heard nothing other than ChOLeSteRoL!!!
The topic of cholesterol being the 'cause' of CardioVascular Disease (CVD) and the use of statins to reduce said cholesterol levels has been front and center in the world of heart disease and has recently become a hotly debated topic...
For me, I wanted to know what all of the 'issues' are with cholesterol- I mean, if I am going to take a medicine (statin, for instance) to reduce my cholesterol, I want to know all about why I am doing it... The side effects of those meds aren't small or insignificant...
So, I started looking at cholesterol's role in the body, how it is produced and metabolized, and where it can go wrong. What follows is, more or less, a running diary of things I've come across along with some notes about my thoughts.
As always- I welcome comment and input...
Start Here- a quick primer of what this page is all about
Lipid Transport
Here's the major players:
- Triglycerides
- Micelles
- Chylomicrons
- Lipase
- LPL
- VLDL
- IDL
- LDL
- HDL
- Apoliporotein B48
- Apoliporotein C2
- Apoliporotein E
- Apoliporotein A1
- Apoliporotein B100
(we'll put this all together at the end with a video series)
Let's look at each one
Triglycerides:
Triglycerides- the major form of fat stored by the body. It consists of three arms of fatty acid attached to a glycerol 'head'.
There are two pathways for Triglycerides to enter the body, either by eating dietary fats or produced by the body.
Micelles:
Micelles- tiny packages of fatty acids and mono-glycerides made in the intestine so the they can be absorbed into the intestinal wall
Micelles are created in the intestine when the fat we eat is broken down by bile and other enzymes into very small droplets that are 'packaged' into micelles which then can be absorbed through the intestinal wall.
Chylomicrons:
Chylomicrons: come from dietary fat and carry triglycerides, cholesterol, and fat soluble vitamins throughout the body. They come exclusively from the dietary pathway- created in the cells in the intestines.
Chylomicrons come exclusively from the dietary pathway and are packages of the triglycerides, cholesterol, and fat soluble vitamins. The are produce with an apolipoprotien (B48) and gather the (E) and (C2) apolipoproteins from HDL.
Lipase
Lipase: enzymes that break down triglycerides into free fatty acids and glycerol.
In the context of the human body, evidently, there are multiple types of lipase enzymes that come from multiple sources (saliva, pancreas, liver, other tissues)
The Chylomicron, Micelles, Apolipoprotein (B48) are all associated with the 'exogenous' pathway (the path fats take when we eat them)
VLDL, IDL, LDL, Apolipoprotein (B100) are all associated with the delivery system the liver uses to package up triglycerides and cholesterol for distribution
Lipoprotein Lipase (LPL)
Lipoprotein Lipase (LPL): Lipoprotein lipase (LPL) is an extracellular enzyme on the vascular endothelial surface that degrades circulating triglycerides in the bloodstream. These triglycerides are embedded in very low-density lipoproteins (VLDL) and in chylomicrons that travel through the bloodstream
This bad boy is everywhere, ready to latch up with any thing carrying the Apolipoprotein (C2) which is Chylomicrons and VLDL- and that's because those two 'boats' are loaded with triglycerides meant to be delivered to the cells, and apoC2 latches up with the LPL to break the triglycerides into the base fatty acids and glycerol.
Verly Low Density Lipoprotein (VLDL)
Very Low Density Lipoprotein (VLDL): This is the primary package the liver builds to carry triglycerides, and cholesterol throughout the body. They come exclusively from the liver and are marked with an apolipoprotein (B100) when first created and pick up the (C2) and (E) apolipoproteins shortly after in the bloodstream (from HDL).
VLDL, like Chylomicrons, are meant to deliver big payloads of Triglycerides to the body and use the apolipoprotein (C2) to latch up with the LPL. Once it has done this, it becomes smaller and more dense- an Intermediate Density Lipoprotein (IDL)
Intermediate Density Lipoprotein (IDL)
Intermediate Density Lipoprotein (IDL): are created when VLDLs give up their fatty acids. They’re then either removed by your liver or converted into LDL.
More or less, the VLDL gives up some triglycerides and turns into IDL that can either go on to give more triglycerides to other cells (where it gets smaller, more dense, and turns into LDL) or head back to the liver to get recycled or converted to LDL.
Low Density Lipoprotein (LDL)
Low Density Lipoprotein (LDL): essentially the 'end of the line' product or 'remnant' of what started at VLDL made in the liver. It is made nearly entirely of cholesterol and cholesterol-ethers and has one apolipoprotein left- the (B100). It is also made by the liver as well.
The major role of LDL is to deliver cholesterol to the proper locations in the body (which is nearly everywhere). The apolipoprotein (B100) is the only apolipoprotein on LDL which means it is not taken up into the liver via the apolipoprotein (E) pathway which in turn can leave LDL in circulation for much longer than VLDL or IDL.
A major question I've had is about the final disposition of LDL. The argument is that since no apoE then not taken up in liver but, this guy clears that up for me...
Chylomicrons (from food) and what I'll call the VLDL chain (from the Liver) are associated with how Triglycerides and Cholesterol are distributed throughout the body.
HDL appears to be mostly focused on gathering exccess cholesterol around the body and brining it back to the liver. It also supports the other two processes by sharing apoE and apoC2 with Chylomicrons and VLDL
High Density Lipoprotein (HDL)
High Density Lipoprotein (HDL): HDL transport cholesterol from the tissues of the body to the liver where it is converted to bile. Has additional support roles in the distribution of apolipoproteins to Chylomicrons and VLDL.
In the context of 'too much' cholesterol has been delivered to the individual cells, HDL comes along and gathers it up and takes it to the liver to be recycled into bile- in this way, it removes cholesterol and guards against plaques from starting in those areas.
Apolipoproteins
Apolipoproteins are like keys that have been added to the lipoprotein and gives it access to various things. The chart above summarizes the 5 apolipoproteins and what they do.
Here's a college exam prep series on the subject:
Another great series that explains it a bit differently
The best explation of the overall lipid transport system I've found
OK, so now I've got a few questions...
If apoB100 tagged lipoproteins only come from the liver...
How does eating saturated fat cause LDL to go up?
If LDL is exclusively made by the body (comes from Liver or as IDL remnant that came from Liver), how is it that eating saturated fat causes LDL to go up?
Does that mean eating more saturated fat causes more triglycerides from chylomicron remnants arrive back at liver causing more VLDL packages to be produced?
If it does cause LDL to go up, is that 'expected' and normal- or is that problematic? (is it 'supposed'Â to do that?)
Speaking of 'saturated fat'- what is that?
While the second video does a good job showing the differences between the saturated, unsaturated, and trans fats- it does fall back on the 'increases the 'bad cholesterol' tome and fails to discuss why consuming them raises LDL.
Trans Fats from 'partially hydrogenated' products like margarine were banned, according to this video, in 2018 and that products already produced could be sold up until 2020.  Trans Fats not found in nature very much, trans fats bad.
(Warning: these videos are academic and possibly dry...)
oxidation of fatty acids
oxidation of unsaturated fatty acids
I'm no expert, but here's my thoughts
Seems like there are two main ways for 'cholesterol' (and triglycerides) to get into the blood stream...
You eat it, or, the liver.
Eating it- When you eat fat/cholesterol, it appears to me that the intestines package them up into Chylomicrons with get into the blood stream and deliver triglycerides throughout the body and are eventually taken up by the liver and broken down for further re-packaging and distribution (or use right there in the liver).
The only place Chylomicrons are 'created' is in the intestines as a result of consuming dietary fats and cholesterol.
Liver- The liver packages up triglycerides and cholesterol into special containers referred to as Very Low Density Lipoproteins (VLDL) and also Low Density Lipoproteins (LDL). It sends those out into the blood stream to distribute triglycerides and cholesterol to the many places it is needed.
The only place LDL is 'created' is either directly in the liver or as a 'VLDL remnant' where a VLDL has distributed enough triglycerides and has 'shrunk' down enough to be classified as LDL.
Wait- LDL is 'only' made in the liver, not by eating it, huh?
The base line broadcast from 'the experts' has been:
Eating saturated fat increases blood LDL levels, LDL causes CVD, lower LDL by reduce saturated fat intake and take statins... right?
I don't have an answer for that, so here's some more videos:
(This is a great college test-prep series on the subject)
Let's shift to the 'lipoproteins'...
The base line broadcast from 'the experts' has been:
Eating saturated fat increases blood LDL levels, LDL causes CVD, lower LDL by reduce saturated fat intake and take statins... right?
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