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Various answers in biology SE, including two quite upvoted ones (1, 2) claim that (in humans) returning cholesterol to the liver is done by HDL.

If I understand correctly, Wikipedia's Reverse cholesterol transport page also says this is done by HDL.

However, this blog post (by Peter Attia) says:

Historically this process of returning cholesterol to the liver was thought to be performed only by HDL’s and has been termed reverse cholesterol transport, or RCT [...]

This RCT concept is outdated as we now know LDL’s actually perform the majority of RCT. While the HDL particle is a crucial part of the immensely complex RCT pathway, a not-so-well-known fact is that apoB lipoproteins (i.e., LDL’s and their brethren) carry most of the cholesterol back to the liver. In other words, the “bad” lipoprotein, LDL, does more of the cleaning up (i.e., taking cholesterol back to the liver) than the “good” lipoprotein, HDL!

Which is right?

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1 Answer 1

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According to Reverse Cholesterol Transport: Molecular Mechanisms and the Non-medical Approach to Enhance HDL Cholesterol (Frontiers in Physiology, 2018), both HDL and LDL are involved in reverse cholesterol transport.

reverse cholesterol transport

In short: HDL takes cholesterol from the blood (from lipid-laden macrophages) and delivers it to the liver 1) via scavenger receptors (SR-B1) or 2) via LDL and LDL receptors (LDL-R). (For a detailed explanation of the diagram, see the Figure 1. in the linked article. There's a similar diagram (Fig.1) in Journal of Cardiology.)

Petter Atti says in his blog (emphasis mine):

Historically this process of returning cholesterol to the liver was thought to be performed only by HDL’s and has been termed reverse cholesterol transport, or RCT [...]

This RCT concept is outdated as we now know LDL’s actually perform the majority of RCT. While the HDL particle is a crucial part of the immensely complex RCT pathway, a not-so-well-known fact is that apoB lipoproteins (i.e., LDL’s and their brethren) carry most of the cholesterol back to the liver. In other words, the “bad” lipoprotein, LDL, does more of the cleaning up (i.e., taking cholesterol back to the liver) than the “good” lipoprotein, HDL!

He says that LDL does "more of the cleaning" than HDL, which may be technically correct in the sense that more LDL than HDL particles may be involved, but this alone does not change the concept of good or bad cholesterol. In the image, you can see that the initial cleaning (step 2 and 3) is done only by HDL, so without HDL no cleaning might occur at all.

Low HDL and high LDL levels in the blood are known risk factors for atherosclerosis (NCBI Books, 2019). Not all LDL particles are bad, though, the most harmful are oxidized small dense LDL particles (Hindawi, 2017).

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  • $\begingroup$ I don't think your quote of Peter's blog supports your claim, as Peter only said that more cholesterol is returned to the liver by LDL (than the amount of cholesterol that is returned to the liver by HDL, which is non-zero). The sentence before the one you quoted says, if I understand correctly, that LDL returns cholesterol to the liver.. $\endgroup$ Commented May 7, 2019 at 19:13
  • $\begingroup$ @OrenMilman, I edited the answer completely. $\endgroup$
    – Jan
    Commented May 8, 2019 at 8:22
  • $\begingroup$ Can you elaborate on the difference between uptake of LDL by either Scavenger-Receptor "SCR-B" or LDL-Receptor on liver cells. Must I read "the most harmful are oxidized small dense LDL particles (Hindawi, 2017)", first? Can you expand your answer, as most people I guess do not know that liver cells have the LDL receptors and have never heard of Scavenger Receptor on liver cells (me, only yesterday, before I read you excellent answer). $\endgroup$ Commented Nov 6, 2021 at 16:53
  • $\begingroup$ Great answer! It's pretty much focused on the question, so why not elaborate more about the concept of "cleaning up": those words may not be used for LDL carrying cholesterol that might become oxidized while being carried on LDL? Then, that would be the SCR-B, not the LDL-receptor on liver cells? $\endgroup$ Commented Nov 10, 2021 at 10:50
  • $\begingroup$ Re critique by Oren Milman above: Your last link out, Hindawi, says: "Oxidized LDL is recognized by a number of receptors, including CD36 and TLR-4", thus "cleaning up" in a literal sense you apply seems not to be "done" by LDL. When LDL becomes messy from O2, it does not do any reverse transport any more - itself, needs to be cleaned up, by receptors presumably not located on the liver but on immunce cells. I think that's very interesting, why don't you elaborate. Quote is very difficult to find, as very relevant, reading through the source you gave. $\endgroup$ Commented Nov 10, 2021 at 19:11

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