The assembly of triacylglycerol-rich lipoproteins: an essential role for the microsomal triacylglycerol transfer protein.
Raised plasma triacylglycerol is an independent risk factor for cardiovascular disease, and an understanding of factors which regulate the synthesis and degradation of lipoproteins which carry triacylglycerol in the blood may lead to novel approaches to the treatment of hypertriacylglycerolaemia. An active microsomal triacylglycerol transfer protein (MTP) is essential for the assembly of particles which transport triacylglycerol through the circulation. After absorption in the intestine, dietary fat and fat-soluble vitamins are incorporated into chylomicrons in the intestinal epithelial cells, and these lipoproteins reach the bloodstream via the lymphatic system. Patients with the rare genetic disorder, abetalipoproteinaemia, in which MTP activity is absent, present clinically with fat-soluble vitamin and essential fatty acid deficiency, indicating a key role for MTP in the movement of fat into the body. The triacylglycerol-rich lipoprotein found in fasting blood, VLDL, is assembled in the liver by an MTP-dependent process similar to chylomicron assembly, and transports triacylglycerol to extra-hepatic tissues such as adipose tissue and heart. In the absence of MTP activity, VLDL are not synthesized and only extremely low levels of triacylglycerol are present in the blood. Dietary components, including fat, cholesterol and ethanol, can modify the expression of the MTP gene and, hence, MTP activity. The present review summarizes current knowledge of the role of MTP in the assembly and secretion of triacylglycerol-rich lipoproteins, and the regulation of its activity in both animal and cell systems.
White
D A
DA
School of Biomedical Sciences, University of Nottingham, UK. david.white@nottingham.ac.uk
Bennett
A J
AJ
Billett
M A
MA
Salter
A M
AM
D000012:Abetalipoproteinemia / Q000378:metabolism; D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D053480:Cholesterol Ester Transfer Proteins; D002914:Chylomicrons / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002914:Chylomicrons; D004041:Dietary Fats; D006023:Glycoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D000431:Ethanol