Expansion
Chylomicrons carry dietary fat, VLDL endogenous fat, LDL delivers cholesterol, HDL returns it
Expansion
| Lipoprotein | Origin | Main lipid | Role |
|---|---|---|---|
| Chylomicron | Intestine | Triglyceride | Dietary fat to tissues |
| VLDL | Liver | Triglyceride | Endogenous fat to tissues |
| IDL | VLDL remnant | Intermediate | |
| LDL | IDL | Cholesterol | Delivers cholesterol to tissues |
| HDL | Liver and gut | Cholesterol | Reverse transport back to liver |
Lipoprotein lipase, on capillary endothelium and activated by apoC-II, hydrolyses triglyceride from chylomicrons and VLDL, releasing fatty acids to tissue. Insulin stimulates it, which is why insulin deficiency causes hypertriglyceridaemia.
LDL receptor uptake is the main clearance route; defects cause familial hypercholesterolaemia, with tendon xanthomata and premature coronary disease.
Drug targets
- Statins: inhibit HMG-CoA reductase, the rate-limiting step of cholesterol synthesis; the fall in intracellular cholesterol upregulates LDL receptors, which is the main mechanism of LDL lowering
- Ezetimibe: blocks intestinal absorption
- PCSK9 inhibitors: prevent LDL receptor degradation
- Fibrates: PPAR-alpha agonists, mainly lowering triglyceride