intermediate-density lipoprotein

**Formation and metabolism** - The liver secretes VLDL, which carries endogenous triglycerides (TG) and contains apoB-100, apoC-II, and apoE. - In capillaries of muscle and adipose tissue, lipoprotein lipase (LPL) is activated by apoC-II. It hydrolyzes VLDL TG, which shrinks the particle and makes it denser. The result is IDL (a VLDL remnant). - IDL contains apoB-100 and apoE. It has lost most of its apoC-II. It carries both TG and cholesterol esters. - IDL has two fates: 1. About half is taken up by the liver through receptor-mediated endocytosis. ApoE binds the LDL receptor (apoB-100/E receptor) and LRP1. 2. The rest is further hydrolyzed by hepatic lipase, which removes more TG and produces LDL. LDL carries mostly cholesterol esters and apoB-100 only. - Pathway: VLDL → IDL → LDL.

**Clinical significance** - **Familial dysbetalipoproteinemia (type III hyperlipoproteinemia, "broad beta disease")**: - Cause: homozygous apoE2/E2, which binds the receptor poorly. Chylomicron remnants and IDL accumulate. - Labs: elevated cholesterol and TG. Electrophoresis shows a "broad beta" band. The VLDL-C/TG ratio is >0.3. - Findings: palmar xanthomas (palmar crease; pathognomonic), tuberoeruptive xanthomas, and premature atherosclerosis (coronary and peripheral vascular disease). - Often needs a secondary "second hit" to manifest, such as obesity, diabetes, or hypothyroidism. - Treatment: lifestyle changes, fibrates and/or statins. - **Atherogenicity**: IDL is a small remnant particle that can enter the arterial intima. It is considered atherogenic, similar to LDL and other remnant lipoproteins. - **Hepatic lipase deficiency**: IDL and TG-rich LDL/HDL accumulate. This is rare. - **LPL or apoC-II deficiency** (type I): chylomicron and VLDL accumulation with severe hypertriglyceridemia and pancreatitis. This is distinct from IDL accumulation.

**High-yield comparison of lipoproteins by density (least to most dense)** Chylomicron < VLDL < IDL < LDL < HDL.

**Key points for boards** - IDL is a short-lived intermediate and is not usually measured routinely. - Its uptake depends on apoE. The key apolipoproteins are apoB-100 and apoE. - A buzzword pairing is palmar xanthomas with elevated IDL and chylomicron remnants, which points to apoE2 homozygosity.