Role of apolipoprotein CIII in triglyceride-rich lipoprotein metabolism

Apolipoprotein CIII (ApoCIII) appears to play a key role in triglyceride-rich lipoprotein (TRL) metabolism. This 8.8 kDa polypeptide is mainly synthesized by the liver in 3 isoforms. The gene involved has been mapped on chromosome 11, and several polymorphisms associated with hypertriglyceridaemia and/or coronary artery disease (CAD) have been described. In normolipidaemic individuals, the total plasma ApoCIII level (0.10 g/l) is mainly HDL-linked. Plasma levels are increased in hyper-triglyceridaemic subjects in whom ApoCIII is VLDL-linked. In Type 2 diabetic patients, the ApoCIII concentration varies with metabolic control of the disease but does not always correlate with the triglyceride level. In various clinical studies, the level of VLDL/LDL-linked ApoCIII was correlated with the severity of the CAD score, and treatment with fibrates decreased the ApoCIII mRNA level in association with PPAR activation. Overexpression of the human ApoCIII gene in transgenic animals results in hypertriglyceridaemia, which can be corrected by overexpression of the ApoE gene. ApoCIII decreases TRL catabolism by inhibiting lipoprotein lipase activity and reducing ApoE-dependent hepatic uptake of TRL and remnants. There appears to be an interaction between ApoCIII and ApoE at the surface of the lipoprotein. Our recent study of ApoCIII levels in TRL and intermediate-density lipoprotein isolated from hyperlipidaemic Type III and IV individuals confirmed the importance of the ApoCIII/ApoE ratio in these lipoproteins.