On: Part III of V: HDL, reverse cholesterol transport, CETP inhibitors, and apolipoproteins.
Episode: 22
Date: October 2018
Key Subjects:
- Old school view of cholesterol transport overly simplified:
- Forward cholesterol transport (FCT).
- Delivery of cholesterol by VLDL, LDL and chylomicrons to the cells.
- Reverse cholesterol transport (RCT).
- Return of cholesterol to the liver by HDL.
- Forward cholesterol transport (FCT).
- Leads to erroneous view that HDL is “good” and higher HDL is “better”.
- Forward cholesterol transport observations:
- VLDL and chylomicrons deliver energy (triglycerides and phospholipids) to the cell, not cholesterol (cells make their own).
- Cholesterol is part of the lipoprotein to support its spherical structure.
- After the energy delivery, VLDLs are cleared very quickly.
- Very few stay around and turn into LDL.
- Much LDL is made in and comes from the liver directly.
- LDL is the problem particle as it stays in circulation the longest (days).
- VLDL half life = half an hour.
- VLDL and chylomicrons deliver energy (triglycerides and phospholipids) to the cell, not cholesterol (cells make their own).
- Reverse cholesterol transport observations:
- HDL not just “good”.
- As in, it doesn’t only pick up cholesterol and delivers it back to the liver.
- HDL also transfers cholesterol to other lipoproteins.
- These particles may take it back to the liver (good).
- Or stay in circulation (not good).
- For instance, an LDL particle may get up to 60% of its cholesterol load by bumping into HDL particles.
- All classes of lipoproteins are involved in the reverse transport, not just HDL.
- Cholesterol can be taken to many places.
- Back to the liver, to the intestine or it stays in circulation.
- If you have a high or low level of HDL-C, it tells you very little about the effectiveness of all the different ways in which HDL is active.
- Increasing HDL or inhibiting HDL to LDL cholesterol transfer not beneficial.
- False assumption that higher HDL is good because it results in higher cholesterol clearance.
- CETP inhibitors (stop HDL to LDL cholesterol transfer) have not proven to be beneficial.
- HDL not just “good”.
Key Takeaways:
- Disregard HDL number.
Worth Listening:
- 8/10