Absence of Microsomal Triglyceride Transfer Protein in Individuals with Abetalipoproteinemia

Abstract

Abetalipoproteinemia is a human genetic disease that is characterized by a defect in the assembly or secretion of plasma very low density lipoproteins and chylomicrons. The microsomal triglyceride transfer protein (MTP), which is located in the lumen of microsomes isolated from the liver and intestine, has been proposed to function in lipoprotein assembly. MTP activity and the 88-kilodalton component of MTP were present in intestinal biopsy samples from eight control individuals but were absent in four abetalipoproteinemic subjects. This finding suggests that a defect in MTP is the basis for abetalipoproteinemia and that MTP is indeed required for lipoprotein assembly.

Overproduction of intestinal lipoprotein containing apolipoprotein B-48 in Psammomys obesus: impact of dietary n-3 fatty acids

“…The suppression of apo B-48 was not due to changes in apo B transcription, since Apob 48 mRNA levels were unaffected. It also did not involve MTP, an essential component in apo-B-48-containing lipoprotein assembly and secretion [51]. One possible explanation may be the limiting availability of triglycerides, phospholipids and cholesteryl esters that are known to protect apo B-48 from proteasome degradation.…”

Hepatic microsomal triglyceride transfer protein messenger RNA concentrations are increased by dietary cholesterol in hamsters

“…It is possible that increased amounts of MTP are required to transfer the increased amount of lipid to the maturing lipoprotein particle. Functional MTP appears to be required for VLDL production [2], facilitating both translocation of apoB across the endoplasmic reticulum and its association with lipid [14][15][16] and MTP appears to be rate limiting for these processes in cultured cells [17,18]. However, reduced VLDL output in vivo does not appear to be associated with reduced MTP activity [7].…”

“…Support for a critical role for the protein in vivo is provided by patients with abetalipoproteinaemia. Such patients lack functional MTP, due to defects in the MTP gene and are unable to assemble or secrete chylomicrons and VLDL [2]. The human and hamster MTP genes have been cloned and the promoter sequences shown to contain a negative insulin response element and modified sterol response element [3].…”

Cholesterol absorption status and fasting plasma cholesterol are modulated by the microsomal triacylglycerol transfer protein −493 G/T polymorphism and the usual diet in women

“…Indeed, it is able to transfer cholesterol esters [13] and triglycerides from the endoplasmic reticulum membranes to nascent apo-B lipoproteins [46]. For instance, the loss of activity resulting from mutations in the coding regions of the MTP gene expresses the rare genetic disorder abetalipoproteinemia, with a suppressed chylomicron secretion and hypocholesterolemia [40,45]. The MTP gene is polymorphic, with several genetic variants especially in the promoter region [14,17].…”