HDL cholesterol is a reading shown on your lipid panel along side – total, LDL, and VLDL cholesterol. The higher the amount of HDL…the better it is for health and it varies with other cholesterol numbers. It is a support system needed in our body to metabolise lipids as it carries important proteins. Hence the importance.

However, when I studied the HDL numbers in the reports of my local clients and  compared it with international case studies; I did not find the numbers corresponding very well even though the base parameters look the same. So what drives HDL numbers? Does genetics play a role in driving the HDL numbers?

 

HDL

(Study reference: https://www.sciencedirect.com/science/article/pii/S0146280607000059)

Let us first look at why HDL numbers are important and yet, they don’t seem (to me) relevant in the entire context.

Ques: Does HDL plasma numbers are good indicators of CHD (coronary heart disease)?

Ans: HDL functionality depends on: Metabolism, kinetics, concentration of various HDL subclasses, & genetic factors. All these may contribute to anti-atherogenic properties of HDL and therefore, standard plasma measurement may not capture the full range of HDL affects. (Study reference: https://www.sciencedirect.com/science/article/pii/S0146280607000059)

Ques: Treating low HDL levels in sub-groups of patients?

Ans: No formal HDL treatment guidelines ’cause of lack of strong clinical evidence to support effective pharmacologic therapy.

 

Chylomicrons Large particles that carry dietary lipid. Associated with apo A-I, A-II, A-IV, B-48, C-I, C-II, C-III, and E.
VLDL Carries TG made by the liver and some LDL particles. Associated with apo lipoproteins B-100, C-II, C-III, and E.
IDL Breakdown product of VLDL-C. Carries cholesterol esters and TGs.
LDL Core of cholesterol esters, small TGs surrounded by free cholesterol, phospholipids, and apolipoprotein B-100. Delivers cholesterol to tissues.
HDL Carries cholesterol esters, associated with apo A-I, A-II, C-I, C-II, C-III, D, and E.

If we look at Chylomicrons (first in the chain) & HDL (support system) proteins, they look no different from each other and yet they have different metabolic pathways and roles in lipid metabolisation.

Let us study the process:

  • HDL is synthesised by both liver & intestine
  • Apo A1 acquire free cholestrol for peripheral cells via ABCA 1
  • Free cholestrol is then esterified within HDL particle via LCAT
  • HDL cholestrol esters are taken by liver for Bile excretion via scavenger receptor  B1 OR cholestrol esters can be transfered to lipoproteins and returned to liver
  • Several TG lipase gene family members are involved in metabolism of HDL
  • Hepatic & endothelial lipases hydrolyze HDL, TG & phospholipids

*Cholesterol ester is storage form of cholesterol

Approximate distribution of protein, cholesterol and tryglycerides across lipo proteins

Chylomicron VLDL IDL LDL HDL
Protein 1% 10% 10% 20% 50%
TAG 90% 55% 30% 15% 15%
Cholesterol 1% 10% 10% 10% 5%
Cholesterol Ester 3% 15% 35% 50% 30%

Now let us look into the processing of Chylomicrons to LDL to study if there is any factor that derives HDL numbers and do not touch LDL numbers?

  • a) HDL donates Apo E & Apo CII to Chylomicron for it to be processed in liver.
  • b) TAG + Ch gets repackaged via Protein ApoB100 to form VLDL in the liver
  • c) VLDL enters the blood and HDL again delivers CII and E to process it further.
  • d) Apo CII is taken back by HDL and a part of the remnant VLDL which is now IDL enters liver via Apo E/receptor and a part comes back into circulation
  • e) IDL returns Apo E back to HDL and turn into LDL
  • f) HDL is getting back both Apo CII & Apo E in the process through out the cycle

In entire cycle from Chylomicron to LDL; HDL plays a support role.

Now my question to you is this:

Ques: Processing of TAG demand bile secretion via liver &/or gallblader and low TAG numbers and higher LDL numbers should be a good indicator for this process. Doesn’t this prove good processing of HDL in liver? 

Ques: If my TAG and LDL levels numbers are good showing a progress metabolically – low TAG and high LDL numbers, then why should I be worried about HDL?

Ques: Doesn’t my LDL levels are a proof that HDL are working fine because they won’t be in place without HDL support?

Ques: Why should I be even be looking at HDL levels when there is no other way to produce LDL without HDL?

Ques: What drives HDL numbers?

Ques: And why it may not be in sync with other lipoproteins whereas it mostly carries same proteins as chylomicrons and react with same lipases or receptors as the rest of lipoproteins?

What am I missing in the riddle?

Umesh Chhikara

Sports Scientist