What is the physiology of lipids and lipoproteins?

Updated: Jun 27, 2019
  • Author: Henry J Rohrs, III, MD; Chief Editor: Stuart Berger, MD  more...
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The two major forms of circulating lipid in the body, triglyceride (TG) and cholesterol, are insoluble in plasma. However, these lipids can be transported throughout the bloodstream as lipoproteins when packaged with phospholipids and proteins (apoproteins). Lipoproteins have an outer core of cholesterol, phospholipids, and apoproteins and an inner core composed of TG and cholesterol ester (CE). Apoproteins function as (1) structural proteins, (2) proteins that make the lipoprotein particle soluble, (3) enzyme activators (eg, apoprotein C-II activates lipoprotein lipase [LPL], apoprotein A-I activates lecithin-cholesterol acyltransferase [LCAT]), and (4) ligands for receptors (eg, apoprotein B-100 binds to the low-density lipoprotein receptor [LDL-R], which is also known as the apoprotein B-100 – apoprotein E receptor).

Lipoproteins have been classified into five major classes, as depicted in the table below.

Table 1. Biology of Lipoproteins (Open Table in a new window)


Major Lipid Composition

Role in Normal Fasting Plasma

Measured Substance

High-density lipoprotein cholesterol (HDL-C)


Antiatherogenic (involved in reverse cholesterol transport from the tissues to the liver)


Low-density lipoprotein cholesterol (LDL-C)


Major cholesterol carrier

Can be measured directly (direct LDL-C) or can be calculated*

Intermediate-density lipoprotein cholesterol (IDL-C)

TG and cholesterol

Intermediate between very low-density lipoprotein (VLDL) and LDL

Not routinely measured; can be assessed by lipoprotein electrophoresis (LPE) or measured by ultracentrifugation



Major TG carrier





Not routinely measured; can be assessed by LPE or measured by ultracentrifugation

* Calculated using the Friedewald equation: LDL-C = Total cholesterol (TC) - HDL-C - TG/5

TG/5 is the estimate of the VLDL-C. 


The classes of lipoprotein are not homogeneous in size or composition. For example, low-density lipoprotein cholesterol (LDL-C) can be divided into cholesterol-rich light, or buoyant, LDL-C and cholesterol-depleted, or dense, LDL-C. Dense LDL-C is more atherogenic than light LDL-C.

Lipoproteins are derived from the exogenous and the endogenous pathways. In the exogenous pathway, dietary lipids are consumed with meals; these lipids (predominantly TGs) are packaged by the intestinal mucosal cells into chylomicrons. Chylomicrons, which are TG rich, enter the lymphatic system. The thoracic duct empties into the vena cava, and chylomicrons systemically circulate. Apoprotein C-II, apoprotein B-48, and apoprotein E are the clinically important apoproteins of chylomicrons.

Apoprotein B-48 is a chylomicron structural protein. Chylomicrons bind to LPL via apoprotein C-II. Once acted on by LPL, which is attached to the luminal side of the capillary endothelium adjacent to muscle and adipose tissue, chylomicrons release TGs as monoglycerides and free fatty acids. Defects in apoprotein C-II or LPL can lead to defects in chylomicron clearance. Muscle normally burns the free fatty acids and monoglycerides for energy. Resynthesized TGs can be used for plasma and cell organelle membrane synthesis. Adipose tissue uses free fatty acids and monoglycerides to resynthesize TGs that are stored for future energy needs. As an alternative, adipocytes can use TGs in membrane synthesis, which is similar to muscle.

When the chylomicrons are reduced in TG content, they become remnants that are rapidly cleared by the liver (apoprotein E binds to the LDL receptor [LDL-R]). At this time, apoprotein C-II is passed to high-density lipoprotein (HDL) particles in the circulation. In the fasting state, chylomicrons and chylomicron remnants are not normally detected in plasma.

In the endogenous pathway, the liver produces VLDL. The clinically important apoproteins in VLDL are apoprotein C-II, apoprotein B-100, and apoprotein E. Like chylomicrons, VLDL interacts with LPL via apoprotein C-II to release TG, forming intermediate-density lipoprotein (IDL) particles. With the formation of IDL, apoprotein C-II is transferred to HDL particles. IDL particles are rapidly removed by the liver via apoprotein E interaction with the LDL-R. IDL particles may be further metabolized to LDL by continued removal of TG by hepatic lipase.

In the conversion from IDL to LDL, apoprotein E is shed and is picked up by HDL particles. LDL is removed by binding to the LDL-R. Approximately two thirds of circulating LDL is removed by the liver, and approximately one third is removed by extrahepatic tissues, including steroid-producing cells and cells within the subintimal space in which atheromatous plaques develop. In the subintimal space, the protective effect of circulating antioxidants is lost, and LDL is oxidized.

Oxidized LDL is removed by the scavenger receptor, which is different from the LDL-R. Smooth muscle cells and macrophages express scavenger receptors. This uptake of LDL is not regulated, and macrophages and smooth muscle cells can take up so much oxidized LDL and cholesterol that they become foam cells. Because oxidized LDL is toxic to cells, it can lead to early endothelial injury, allowing platelet adhesion and localized release of platelet-derived growth factor (PDGF). In contrast, when other cells have sufficient cholesterol, they down-regulate the LDL-R to decrease cholesterol uptake into the cell.

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