The 17th Annual Meeting of the European Lipoprotein Club

Abstract

The European Lipoprotein Club met September 12-15, 1994, in Tutzing, Germany. There were 92 participants from 12 European countries and the United States. Dr John Wetterau of Bristol-Myers Squibb Pharmaceutical Research Institute opened the meeting with a State of the Art Lecture entitled “The Microsomal Triglyceride Transfer Protein: Characterization and Role in the Assembly of VLDL and Chylomicrons.” The microsomal triglyceride transfer protein (MTP) is a soluble lipid transfer protein found in the lumen of microsomes of liver and intestine. This heterodimer is composed of the multifunctional protein disulfide isomerase and a unique large subunit of molecular weight 97 000. In vitro, MTP catalyzes the transport of triglyceride, cholesteryl ester, and a variety of phospholipids between membranes. When one compares the fractional transfer rates, MTP appears to selectively bind and transport hydrophobic neutral lipid. However, the assays used to characterize MTP have at least 100-fold more phospholipid than neutral lipid, so in these assays, MTP actually transports more phospholipid than neutral lipid. Abetalipoproteinemia is an autosomal recessive disease in which the subjects have a defect in the assembly and secretion of VLDL and chylomicrons. Recent studies by Dr Wetterau of abetalipoproteinemic subjects showed that MTP activity and the unique large subunit were absent in all four unrelated subjects studied. Frame shift, nonsense, and point mutations that explain the absence of MTP were found in these four subjects. These studies indicated that an absence of MTP function causes abetalipoproteinemia and that MTP is required for the assembly of apoB–containing lipoproteins. Hela cells normally do not synthesize and secrete apoB–containing lipoproteins. When Hela cells were stably transfected with MTP, they were able to efficiently synthesize and secrete apoB-53 particles with a buoyant density of HDL or LDL. Both the level of apoB secretion and the density of the particles formed were regulated …